Jordan S, Koprivica
V, Chen R, Tottori K, Kikuchi T, Altar CA.
The antipsychotic aripiprazole
is a potent, partial agonist at the human 5-HT(1A) receptor.
Eur J Pharmacol 2002 Apr 26;441(3):137-40
a novel antipsychotic with partial agonist activity at dopamine D2 receptors,
bound with high affinity to recombinant human 5-HT(1A) receptors (h5-HT(1A)) in
Chinese hamster ovary cell membranes and displayed potent, partial agonism at
5-HT(1A) receptors in a guanosine-5'-O-(3-[(35)S]thio)-triphosphate ([(35)S]GTP
gamma S)-binding assay that was blocked completely by a selective 5-HT(1A) receptor
antagonist. An interaction with 5-HT(1A) receptors may contribute to the overall
efficacy of aripiprazole against symptoms of schizophrenia, including anxiety,
depression, cognitive and negative symptoms, and to its favorable side-effect
profile. Combined with previous studies demonstrating the potent partial agonism
of aripiprazole at dopamine D2 receptors, this study suggests aripiprazole is
the first dopamine-serotonin system stabilizer." [Abstract]
J, Li Z, Dai J, Meltzer HY.
Atypical antipsychotic drugs, quetiapine,
iloperidone, and melperone, preferentially increase dopamine and acetylcholine
release in rat medial prefrontal cortex: role of 5-HT(1A) receptor agonism.
Brain Res 2002 Nov 29;956(2):349-57
"Preferential increases in both cortical
dopamine (DA) and acetylcholine (ACh) release have been proposed to distinguish
the atypical antipsychotic drugs (APDs) clozapine, olanzapine, risperidone and
ziprasidone from typical APDs such as haloperidol. Although only clozapine and
ziprasidone are directly acting 5-HT(1A) agonists, WAY100635, a selective 5-HT(1A)
antagonist, partially attenuates these atypical APD-induced increases in cortical
DA release that may be due to combined 5-HT(2A) and D(2) blockade. However, WAY100635
does not attenuate clozapine-induced cortical ACh release. The present study determined
whether quetiapine, iloperidone and melperone, 5-HT(2A)/D(2) antagonist atypical
APDs, also increase cortical DA and ACh release, and whether these effects are
related to 5-HT(1A) agonism. Quetiapine (30 mg/kg), iloperidone (1-10 mg/kg),
and melperone (3-10 mg/kg) increased DA and ACh release in the medial prefrontal
cortex (mPFC). Iloperidone (10 mg/kg) and melperone (10 mg/kg), but not quetiapine
(30 mg/kg), produced an equivalent or a smaller increase in DA release in the
nucleus accumbens (NAC), respectively, compared to the mPFC, whereas none of them
increased ACh release in the NAC. WAY100635 (0.2 mg/kg), which alone did not affect
DA or ACh release, partially attenuated quetiapine (30 mg/kg)-, iloperidone (10
mg/kg)- and melperone (10 mg/kg)-induced DA release in the mPFC. WAY100635 also
partially attenuated quetiapine (30 mg/kg)-induced ACh release in the mPFC, but
not that induced by iloperidone (10 mg/kg) or melperone (10 mg/kg). These results
indicate that quetiapine, iloperidone and melperone preferentially increase DA
release in the mPFC, compared to the NAC via a 5-HT(1A)-related mechanism. However,
5-HT(1A) agonism may be important only for quetiapine-induced ACh release."
Ichikawa, Junji, Ishii, Hideo, Bonaccorso, Stefania, Fowler, Wiley L., O'Laughlin,
Ian A., Meltzer, Herbert Y.
5-HT2A and D2 receptor blockade increases
cortical DA release via 5-HT1A receptor activation: a possible mechanism of atypical
antipsychotic-induced cortical dopamine release
2001 76: 1521-1531
"Atypical antipsychotic drugs (APDs), all of which
are relatively more potent as serotonin (5-HT)2A than dopamine D2 antagonists,
may improve negative symptoms and cognitive dysfunction in schizophrenia, in part,
via increasing cortical dopamine release. 5-HT1A agonism has been also suggested
to contribute to the ability to increase cortical dopamine release. The present
study tested the hypothesis that clozapine, olanzapine, risperidone, and perhaps
other atypical APDs, increase dopamine release in rat medial prefrontal cortex
(mPFC) via 5-HT1A receptor activation, as a result of the blockade of 5-HT2A and
D2 receptors. M100907 (0.1 mg/kg), a 5-HT2A antagonist, significantly increased
the ability of both S()-sulpiride (10 mg/kg), a D2 antagonist devoid of
5-HT1A affinity, and R(+)-8-OH-DPAT (0.05 mg/kg), a 5-HT1A agonist, to increase
mPFC dopamine release. These effects of M100907 were abolished by WAY100635 (0.05
mg/kg), a 5-HT1A antagonist, which by itself has no effect on mPFC dopamine release.
WAY100635 (0.2 mg/kg) also reversed the ability of clozapine (20 mg/kg), olanzapine
(1 mg/kg), risperidone (1 mg/kg), and the R(+)-8-OH-DPAT (0.2 mg/kg) to increase
mPFC dopamine release. Clozapine is a direct acting 5-HT1A partial agonist, whereas
olanzapine and risperidone are not. These results suggest that the atypical APDs
via 5-HT2A and D2 receptor blockade, regardless of intrinsic 5-HT1A affinity,
may promote the ability of 5-HT1A receptor stimulation to increase mPFC DA release,
and provide additional evidence that coadministration of 5-HT2A antagonists and
typical APDs, which are D2 antagonists, may facilitate 5-HT1A agonist activity."
Serres, F., Li, Q., Garcia, F., Raap, D. K., Battaglia,
G., Muma, N. A., Van de Kar, L. D.
Evidence That Gz-Proteins Couple
to Hypothalamic 5-HT1A Receptors In Vivo
J. Neurosci. 2000
20: 3095-3103 [Full
Storring, John M., Charest, Alain, Cheng,
Peihua, Albert, Paul R.
TATA-Driven Transcriptional Initiation and
Regulation of the Rat Serotonin 5-HT1A Receptor Gene
Neurochem 1999 72: 2238-2247 [Abstract]
Christopher L. Parks, and Thomas Shenk
The Serotonin 1a Receptor Gene Contains a TATA-less Promoter that Responds
to MAZ and Sp1
J. Biol. Chem. 271: 4417-4430, February
23, 1996. [Full Text]
Xiao-Ming Ou, Hamed Jafar-Nejad, John M. Storring, Juan-Hong
Meng, Sylvie Lemonde, and Paul R. Albert
Novel Dual Repressor Elements
for Neuronal Cell-specific Transcription of the Rat 5-HT1A Receptor Gene
J. Biol. Chem. 275: 8161-8168, March 17, 2000. [Full
D A Bayliss, M Umemiya, A J Berger
Inhibition of N- and P-type calcium currents and the after-hyperpolarization
in rat motoneurones by serotonin
JOURNAL OF PHYSIOLOGY
-LONDON THEN CAMBRIDGE- , 485 ( Pt 3)():635-647 1995 [Abstract]
F, Suhara T, Nakayama T, Ichimiya T, Okubo Y, Takano A, Ando T, Inoue M, Maeda
J, Suzuki K.
Inhibitory effect of hippocampal 5-HT1A receptors on
human explicit memory.
Am J Psychiatry 2003 Feb;160(2):334-40
James E., McCormick, David A.
Neuromodulatory Role of Serotonin
in the Ferret Thalamus
J Neurophysiol 2002 87: 2124-2136
"The magnitude of the hyperpolarizing response decreased with age and varied
greatly across and somewhat within nuclei maintaining the following relationship
(in descending order of magnitude): lateral posterior, lateral dorsal, pulvinar,
mediodorsal, center median, anteroventral, central lateral, ventral basal, and
medial geniculate. This hyperpolarization is elicited through two mechanisms:
one direct and the other via local interneurons. The direct action occurs through
an increase in potassium conductance mediated through the 5-HT1A receptor."
Lora K. Heisler, Hung-Ming Chu, Thomas J. Brennan,
Jean A. Danao, Preetpaul Bajwa, Loren H. Parsons, and Laurence H. Tecott
Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor
PNAS 95: 15049-15054, December 8, 1998. [Full
Greenwood BN, Foley TE, Day HE, Campisi
J, Hammack SH, Campeau S, Maier SF, Fleshner M.
prevents learned helplessness/behavioral depression: role of dorsal raphe serotonergic
J Neurosci. 2003 Apr 1;23(7):2889-98.
(5-HT) neurons in the dorsal raphe nucleus (DRN) are implicated in mediating learned
helplessness (LH) behaviors, such as poor escape responding and expression of
exaggerated conditioned fear, induced by acute exposure to uncontrollable stress.
DRN 5-HT neurons are hyperactive during uncontrollable stress, resulting in desensitization
of 5-HT type 1A (5-HT1A) inhibitory autoreceptors in the DRN. 5-HT1A autoreceptor
downregulation is thought to induce transient sensitization of DRN 5-HT neurons,
resulting in excessive 5-HT activity in brain areas that control the expression
of learned helplessness behaviors. Habitual physical activity has antidepressant/anxiolytic
properties and results in dramatic alterations in physiological stress responses,
but the neurochemical mediators of these effects are unknown. The current study
determined the effects of 6 weeks of voluntary freewheel running on LH behaviors,
uncontrollable stress-induced activity of DRN 5-HT neurons, and basal expression
of DRN 5-HT1A autoreceptor mRNA. Freewheel running prevented the shuttle box escape
deficit and the exaggerated conditioned fear that is induced by uncontrollable
tail shock in sedentary rats. Furthermore, double c-Fos/5-HT immunohistochemistry
revealed that physical activity attenuated tail shock-induced activity of 5-HT
neurons in the rostral-mid DRN. Six weeks of freewheel running also resulted in
a basal increase in 5-HT1A inhibitory autoreceptor mRNA in the rostral-mid DRN.
Results suggest that freewheel running prevents behavioral depression/LH and attenuates
DRN 5-HT neural activity during uncontrollable stress. An increase in 5-HT1A inhibitory
autoreceptor expression may contribute to the attenuation of DRN 5-HT activity
and the prevention of LH in physically active rats." [Abstract]
X, Kushwaha N, Albert PR, Penington NJ.
A critical protein kinase
C phosphorylation site on the 5-HT(1A) receptor controlling coupling to N-type
J Physiol 2002 Jan 1;538(Pt 1):41-51
Elaine, Carr, I. Craig, Milligan, Graeme
Regulation of G Protein
Activation and Effector Modulation by Fusion Proteins between the Human 5-Hydroxytryptamine1A
Receptor and the alpha Subunit of Gi1alpha : Differences in Receptor-Constitutive
Activity Imparted by Single Amino Acid Substitutions in Gi1alpha
Pharmacol 1999 56: 684-692 [Full
Xiang Cai, Zhenglin Gu, Ping Zhong, Yong
Ren, and Zhen Yan
Serotonin 5-HT1A receptors regulate AMPA receptor
channels through inhibiting CaMKII in prefrontal cortical pyramidal neurons
JBC Papers in Press published on July 30, 2002 as 10.1074/jbc.M203752200
Pan L, Gilbert F.
of 5-HT1A receptor subtype in the paraventricular nuclei of the hypothalamus induces
CRH and ACTH release in the rat.
C, Hamon M, Benoliel JJ.
Prevention by 5-HT1A receptor agonists
of restraint stress- and yohimbine-induced release of cholecystokinin in the frontal
cortex of the freely moving rat.
"In line with the idea that cholecystokinin (CCK) is
involved in anxiety-related behaviours, previous investigations showed that stressful
conditions and an 'anxiogenic' drug, yohimbine, increased the cortical release
of CCK like-material (CCKLM) in awake rats, and that this effect could be prevented
by diazepam. Here, we investigated whether other anxiolytic drugs such as 5-HT1A
receptor agonists could also affect cortical CCKLM release. Indeed, neither buspirone
(1 mg/kg i.p.), alnespirone (1 mg/kg i.p.) nor lesopitron (3 mg/kg i.p.) affected,
on their own, CCKLM release. However, pretreatment with the latter drugs completely
abolished the stimulatory effect of restraint stress on the peptide outflow. As
expected of the involvement of 5-HT1A receptors, tertatolol (10 mg/kg i.p) markedly
reduced the inhibitory effect of buspirone on restraint stress-evoked CCKLM overflow.
On the other hand, pretreatment with buspirone, alnespirone or lesopitron also
inhibited the stimulatory effect of yohimbine (5 mg/kg i.p.) on cortical CCKLM
outflow. These data support the idea that the anxiolytic action of 5-HT1A receptor
agonists could be mediated, at least partly, through their inhibitory influence
on cortical CCK-ergic systems." [Abstract]
Meltzer HY, Maes M.
Effects of ipsapirone
on plasma cortisol and body temperature in major depression.
Psychiatry 1995 Oct 1;38(7):450-7 [Abstract]
W.J., Klaassen T, Honig A, Van Praag, H.M.
5-HT Challenge and cognition
in major depression and healthy control subjects
Psychopharmacology Unit Universiteit Maastricht [Poster]
Ou, Hamed Jafar-Nejad, John M. Storring, Juan-Hong Meng, Sylvie Lemonde, and Paul
Novel Dual Repressor Elements for Neuronal Cell-specific
Transcription of the Rat 5-HT1A Receptor Gene
Chem. 275: 8161-8168, March 17, 2000. [Full
Xiao-Ming Ou, John M. Storring, Neena Kushwaha,
and Paul R. Albert
Heterodimerization of Mineralocorticoid and
Glucocorticoid Receptors at a Novel Negative Response Element of the 5-HT1A Receptor
J. Biol. Chem. 276: 14299-14307, April 27, 2001.
Watanabe_K_-I, Ashby_C_R_Jr, Katsumori_H, Minabe_Y, Watanabe, K.
I., Ashby Jr., C. R., Katsumori, H., Minabe, Y.
The effect of the
acute administration of various selective 5-HT receptor antagonists on focal hippocampal
seizures in freely-moving rats
European journal of pharmacology,
398(2):239-246 2000 [Abstract]
Abdouh, John M. Storring, Mustapha Riad, Yves Paquette, Paul R. Albert, Elliot
Drobetsky, and Edouard Kouassi
Transcriptional Mechanisms for Induction
of 5-HT1A Receptor mRNA and Protein in Activated B and T Lymphocytes
J. Biol. Chem. 276: 4382-4388, February 9, 2001. [Full
Wu, X., Kushwaha, N., Albert, P. R., Penington,
A critical protein kinase C phosphorylation site on the 5-HT1A
receptor controlling coupling to N-type calcium channels
Physiol (Lond) 2002 538: 41-51 [Abstract]
Qian, Wichems, Christine, Heils, Armin, Lesch, Klaus-Peter, Murphy, Dennis L.
Reduction in the Density and Expression, But Not G-Protein Coupling, of Serotonin
Receptors (5-HT1A) in 5-HT Transporter Knock-Out Mice: Gender and Brain Region
J. Neurosci. 2000 20: 7888-7895 [Full
Kellett, Elaine, Carr, I. Craig, Milligan,
Regulation of G Protein Activation and Effector Modulation
by Fusion Proteins between the Human 5-Hydroxytryptamine1A Receptor and the alpha
Subunit of Gi1alpha : Differences in Receptor-Constitutive Activity Imparted by
Single Amino Acid Substitutions in Gi1alpha
1999 56: 684-692 [Full
Maria N. Garnovskaya, Thomas W. Gettys,
Tim van Biesen, Veronica Prpic, J. Kurt Chuprun, and John R. Raymond
5-HT1A Receptor Activates Na+/H+ Exchange in CHO-K1 Cells through GiAlpha2
J. Biol. Chem. 272: 7770-7776, March 21,
1997. [Full Text]
DY, Beck SG.
5-HT1A receptor linked to inward-rectifying potassium
current in hippocampal CA3 pyramidal cells.
1994 Jun;71(6):2161-7 [Abstract]
JK, Yan Q, Dawson G, Banerjee P.
Cell-specific regulation of the
stably expressed serotonin 5-HT1A receptor and altered ganglioside synthesis.
Biochim Biophys Acta 1996 Feb 2;1310(2):201-11 [Abstract]
Timothy, Francis, Nicole, Fyodorov, Dmitry, Deneris, Evan S.
ETS Domain Factor Pet-1 Is an Early and Precise Marker of Central Serotonin Neurons
and Interacts with a Conserved Element in Serotonergic Genes
Neurosci. 1999 19: 10348-10356 [Full
Overstreet DH, Daws LC, Schiller GD, Orbach
J, Janowsky DS.
Cholinergic/serotonergic interactions in hypothermia:
implications for rat models of depression.
Behav 1998 Apr;59(4):777-85 [Abstract]
Y, Benavides, J, Scatton, B
Potential mechanisms involved in the
negative coupling between serotonin 5-HT1A receptors and carbachol-stimulated
phosphoinositide turnover in the rat hippocampus.
1991 56: 1276-1285 [Abstract]
Paola M. C., Ghahremani, Mohammad H., Morris, Stephen J., Albert, Paul R.
A Conserved Threonine Residue in the Second Intracellular Loop of the 5-Hydroxytryptamine
1A Receptor Directs Signaling Specificity
1997 52: 164-171 [Full
Talley, Edmund M., Sadr, Negar N., Bayliss,
Postnatal Development of Serotonergic Innervation, 5-HT1A
Receptor Expression, and 5-HT Responses in Rat Motoneurons
Neurosci. 1997 17: 4473-4485 [Full
Ya Fang Liu, Mohammad H. Ghahremani, Mark
M. Rasenick, Karl H. Jakobs, and Paul R. Albert
cAMP Synthesis by Gi-coupled Receptors upon Ablation of Distinct G(Alpha)i Protein
Expression. Gi SUBTYPE SPECIFICITY OF THE 5-HT1A RECEPTOR
J. Biol. Chem. 274: 16444-16450, June 4, 1999 [Full
Garcia-Osta, Ana, Frechilla, Diana, Del
Effect of p-Chloroamphetamine on 5-HT1A and 5-HT7 Serotonin
Receptor Expression in Rat Brain
J Neurochem 2000 74: 1790-1797 [Abstract]
JK, Chromy, BA, Boyers, MJ, Dawson, G, Banerjee, P
the serotonin1A receptor in neuronal cells during prolonged stress and degeneration
J Neurochem 1996 66: 2361-2372 [Abstract]
Yahong, D'Souza, Deborah, Raap, Dani K., Garcia, Francisca, Battaglia, George,
Muma, Nancy A., Van de Kar, Louis D.
Characterization of the Functional
Heterologous Desensitization of Hypothalamic 5-HT1A Receptors after 5-HT2A Receptor
J. Neurosci. 2001 21: 7919-7927 [Abstract]
Protein kinase C induces phosphorylation and desensitization
of the human 5-HT1A receptor
J. Biol. Chem. 266: 14747-14753,
Aug, 1991. [Abstract/Full
Cai, Zhenglin Gu, Ping Zhong, Yong Ren, and Zhen Yan
5-HT1A receptors regulate AMPA receptor channels through inhibiting CaMKII in
prefrontal cortical pyramidal neurons
JBC Papers in Press
published on July 30, 2002 as 10.1074/jbc.M203752200
"We have studied
the regulation of AMPA receptor channels by serotonin signaling in pyramidal neurons
of prefrontal cortex (PFC). Application of serotonin reduced the amplitude of
AMPA-evoked currents, an effect mimicked by 5-HT1A receptor agonists and blocked
by 5-HT1A antagonists, indicating the mediation by 5-HT1A receptors. The serotonergic
modulation of AMPA receptor currents was blocked by protein kinase A (PKA) activators,
and occluded by PKA inhibitors. Inhibiting the catalytic activity of protein phosphatase
1 (PP1) also eliminated the effect of serotonin on AMPA currents. Furthermore,
the serotonergic modulation of AMPA currents was occluded by application of the
Ca2+/calmodulin-dependent kinase II (CaMKII) inhibitors, and blocked by intracellular
injection of calmodulin or recombinant CaMKII. Application of serotonin or 5-HT1A
agonists to PFC slices reduced CaMKII activity and the phosphorylation of AMPA
receptor subunit GluR1 at the CaMKII site in a PP1-dependent manner. We concluded
that serotonin, by activating 5-HT1A receptors, suppress glutamatergic signaling
through the inhibition of CaMKII, which is achieved by the inhibition of PKA and
ensuing activation of PP1. This modulation demonstrates the critical role of CaMKII
in serotonergic regulation of PFC neuronal activity, which may explain the neuropsychiatric
behavioral phenotypes seen in CaMKII knockout mice." [Abstract/Full
Parks, Patricia S. Robinson, Etienne Sibille, Thomas Shenk, and Miklos Toth
Increased anxiety of mice lacking the serotonin1A receptor
95: 10734-10739, September 1, 1998. [Full
Parsons,, Loren H., Kerr, Tony M., Tecott,
5-HT1A receptor mutant mice exhibit enhanced tonic,
stress-induced and fluoxetine-induced serotonergic neurotransmission
Neurochem 2001 77: 607-617 [Abstract]
Ramboz, Ronald Oosting, Djamel Aït Amara, Hank F. Kung, Pierre Blier, Monica
Mendelsohn, J. John Mann, Dani Brunner, and René Hen
receptor 1A knockout: An animal model of anxiety-related disorder
95: 14476-14481, November 24, 1998. [Full
Tsuji, Minoru, Takeda, Hiroshi, Matsumiya,
Protective effects of 5-HT1A receptor agonists against
emotional changes produced by stress stimuli are related to their neuroendocrine
Br. J. Pharmacol. 2001 134: 585-595
results suggest that activation of the adrenocortical system via 5-HT1A receptors
may facilitate some adaptive mechanism(s) involved in the recognition of and/or
ability to cope with stressful situations." [Abstract]
A;Li, Q;Battaglia, G;Van de Kar, LD
WAY-100635 inhibits 8-OH-DPAT-stimulated
oxytocin, ACTH and corticosterone, but not prolactin secretion
JOURNAL OF PHARMACOLOGY 346: (2-3) 261-266 APR 10 1998
"This study investigated
the effects of increasing doses of a selective 5-HT1A receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)
cyclohexanecarboxamide (WAY-100635) on neuroendocrine responses induced by the
5-HT1A receptor agonist 8-OH-DPAT in adult male rats." [Abstract]
Okuhara, Dayne Y., Beck, Sheryl G.
Alter 5-Hydroxytryptamine1A Receptor-effector Pathway in Hippocampal Subfield
CA3 Pyramidal Cells
J Pharmacol Exp Ther 1998 284: 1227-1233
Sacha Wissink, Onno Meijer, David Pearce, Bart van der Burg,
and Paul T. van der Saag
Regulation of the Rat Serotonin-1A Receptor
Gene by Corticosteroids
J. Biol. Chem. 275: 1321-1326,
January 14, 2000. [Full
Y. J. G. Karten, S. M. Nair, L. van Essen,
R. Sibug, and M. Joëls
Long-term exposure to high corticosterone
levels attenuates serotonin responses in rat hippocampal CA1 neurons
PNAS 96: 13456-13461, November 9, 1999 [Full
Ichikawa, Junji, Meltzer, Herbert Y.
R(+)-8-OH-DPAT, a Serotonin1A Receptor Agonist, Potentiated S(-)-Sulpiride-Induced
Dopamine Release in Rat Medial Prefrontal Cortex and Nucleus Accumbens But Not
J Pharmacol Exp Ther 1999 291: 1227-1232 [Full
Zoltán Sarnyai, Etienne L. Sibille,
Constantine Pavlides, Robert J. Fenster, Bruce S. McEwen, and Miklós Tóth
Impaired hippocampal-dependent learning and functional abnormalities
in the hippocampus in mice lacking serotonin1A receptors
97: 14731-14736, December 19, 2000. [Full
Newman-Tancredi, Adrian, Cussac, Didier,
Marini, Laetitia, Millan, Mark J.
Antibody Capture Assay Reveals
Bell-Shaped Concentration-Response Isotherms for h5-HT1A Receptor-Mediated Galpha
i3 Activation: Conformational Selection by High-Efficacy Agonists, and Relationship
to Trafficking of Receptor Signaling
Mol Pharmacol 2002
62: 590-601 [Abstract]
Kenda L. J., Cropper, Jodie D., Berg, Kelly A., Clarke, William P.
Mechanisms of Regulation of Agonist Efficacy at the 5-HT1A Receptor by Phospholipid-Derived
J Pharmacol Exp Ther 2001 297: 1025-1035
Stanley L., Setya, Shilpy, Johnson-Farley, Nadine N., Cowen, Daniel S.
Differential coupling of 5-HT1 receptors to G proteins of the Gi family
Br. J. Pharmacol. 2002 136: 1072-1078 [Abstract]
Catherine A. Chen, and David R. Manning
of Gi Palmitoylation by Activation of the 5-Hydroxytryptamine-1A Receptor
J. Biol. Chem. 275: 23516-23522, August 4, 2000. [Full
Paul R. Albert, Naghmeh Sajedi, Sylvie Lemonde,
and Mohammad H. Ghahremani
Constitutive Gi2-dependent Activation
of Adenylyl Cyclase Type II by the 5-HT1A Receptor. INHIBITION
BY ANXIOLYTIC PARTIAL AGONISTS
J. Biol. Chem. 274:
35469-35474, December 10, 1999. [Full
Sacha Wissink, Bart van der Burg, Benita
S. Katzenellenbogen, and Paul T. van der Saag
of the Serotonin-1A Receptor by Nuclear Factor-kappa B and Estrogen
Endocrinol. 15: 543-552, 2001. [Full
Darmon, M, Langlois, X, Suffisseau, L, Fattaccini,
CM, Hamon, M
Differential membrane targeting and pharmacological
characterization of chimeras of rat serotonin 5-HT1A and 5-HT1B receptors expressed
in epithelial LLC-PK1 cells.
J Neurochem 1998 71: 2294-2303
Kenda L. J., Cropper, Jodie D., Berg, Kelly A., Clarke, William P.
Mechanisms of Regulation of Agonist Efficacy at the 5-HT1A Receptor by Phospholipid-Derived
J Pharmacol Exp Ther 2001 297: 1025-1035
Megan C., French, Karen L., Seckl, Jonathan R.
Diurnal Rhythms of Serotonin 5-HT2C and Corticosteroid Receptor Gene Expression
in the Hippocampus with Food Restriction and Glucocorticoids
Neurosci. 1997 17: 4056-4065 [Full
Alastair J. Barr, and David R. Manning
Agonist-independent Activation of Gz by the 5-Hydroxytryptamine1A Receptor
Co-expressed in Spodoptera frugiperda Cells. DISTINGUISHING INVERSE
AGONISTS FROM NEUTRAL ANTAGONISTS
J. Biol. Chem.
272: 32979-32987, December 26, 1997. [Full
Lim WK, Myung CS, Garrison JC, Neubig
Receptor-G protein gamma specificity: gamma11 shows unique potency
for A(1) adenosine and 5-HT(1A) receptors.
2001 Sep 4;40(35):10532-41 [Abstract]
Boutrel, Benjamin, Monaca, Christelle, Hen, Rene, Hamon,
Michel, Adrien, Joelle
Involvement of 5-HT1A Receptors in Homeostatic
and Stress-Induced Adaptive Regulations of Paradoxical Sleep: Studies in 5-HT1A
J. Neurosci. 2002 22: 4686-4692 [Abstract]
MT, Chuang JI.
Melatonin potentiates 5-HT1A receptor activation
in rat hypothalamus and results in hypothermia.
Res 2002 Aug;33(1):14-9 [Abstract]
DS, Palmier, C, Colpaert, FC, Pauwels, PJ
Autoradiography of serotonin
5-HT1A receptor-activated G proteins in guinea pig brain sections by agonist-stimulated
J Neurochem 1998 70: 1258-1268 [Abstract]
Mustapha, Watkins, Kenneth C., Doucet, Edith, Hamon, Michel, Descarries, Laurent
Agonist-Induced Internalization of Serotonin-1A Receptors in the Dorsal Raphe
Nucleus (Autoreceptors) But Not Hippocampus (Heteroreceptors)
Neurosci. 2001 21: 8378-8386 [Abstract]
P, Ciaranello RD.
Transcriptional regulation of hippocampal 5-HT1a
receptors by corticosteroid hormones.
Brain Res Mol Brain
Res 1995 Mar;29(1):23-34 [Medline]
Froger, Nicolas, Gardier, Alain M., Moratalla, Rosario, Alberti,
Israel, Lena, Isabelle, Boni, Claudette, De Felipe, Carmen, Rupniak, Nadia M.
J., Hunt, Stephen P., Jacquot, Christian, Hamon, Michel, Lanfumey, Laurence
5-Hydroxytryptamine (5-HT)1A Autoreceptor Adaptive Changes in Substance P (Neurokinin
1) Receptor Knock-Out Mice Mimic Antidepressant-Induced Desensitization
J. Neurosci. 2001 21: 8188-8197 [Abstract].
Daniel S. Cowen, Rebecca S. Sowers, and David R.
Activation of a Mitogen-activated Protein Kinase (ERK2)
by the 5-Hydroxytryptamine1A Receptor Is Sensitive Not Only to Inhibitors of Phosphatidylinositol
3-Kinase, but to an Inhibitor of Phosphatidylcholine Hydrolysis
Biol. Chem. 271: 22297-22300, September 13, 1996. [Full
Gregory J. Della Rocca, Yurii V. Mukhin,
Maria N. Garnovskaya, Yehia Daaka, Geoffrey J. Clark, Louis M. Luttrell, Robert
J. Lefkowitz, and John R. Raymond
Serotonin 5-HT1A Receptor-mediated
Erk Activation Requires Calcium/Calmodulin-dependent Receptor Endocytosis
J. Biol. Chem. 274: 4749-4753, February 19, 1999.
receptors that couple to heterotrimeric guanine nucleotide-binding (G) proteins
mediate rapid activation of the mitogen-activated protein kinases, Erk1 and Erk2.
The Gi-coupled serotonin (5-hydroxytryptamine (5-HT)) 5-HT1A receptor, heterologously
expressed in Chinese hamster ovary or human embryonic kidney 293 cells, mediated
rapid activation of Erk1/2 via a mechanism dependent upon both Ras activation
and clathrin-mediated endocytosis. This activation was attenuated by chelation
of intracellular Ca2+ and Ca2+/calmodulin (CAM) inhibitors or the CAM sequestrant
protein calspermin. The CAM-dependent step in the Erk1/2 activation cascade is
downstream of Ras activation, because inhibitors of CAM antagonize Erk1/2 activation
induced by constitutively activated mutants of Ras and c-Src but not by constitutively
activated mutants of Raf and MEK (mitogen and extracellular signal-regulated kinase).
Inhibitors of the classical CAM effectors myosin light chain kinase, CAM-dependent
protein kinases II and IV, PP2B, and CAM-sensitive phosphodiesterase had no effect
upon 5-HT1A receptor-mediated Erk1/2 activation. Because clathrin-mediated endocytosis
was required for 5-HT1A receptor-mediated Erk1/2 activation, we postulated a role
for CAM in receptor endocytosis. Inhibition of receptor endocytosis by use of
sequestration-defective mutants of -arrestin1 and dynamin attenuated 5-HT1A receptor-stimulated
Erk1/2 activation. Inhibition of CAM prevented agonist-dependent endocytosis of
epitope-tagged 5-HT1A receptors. We conclude that CAM-dependent activation of
Erk1/2 through the 5-HT1A receptor reflects its role in endocytosis of the receptor,
which is a required step in the activation of MEK and subsequently Erk1/2."
Y., Segal, M.
Serotonin 5-HT1A Receptors Modulate Hippocampal Reactivity
to Afferent Stimulation
J. Neurosci. 1997 17: 5591-5598
Daniel S., Molinoff, Perry B., Manning, David R.
Receptor-Mediated Increases in Receptor Expression and Activation of Nuclear Factor-kappa
B in Transfected Chinese Hamster Ovary Cells
1997 52: 221-226 [Full
Li, Qian, Wichems, Christine, Heils, Armin,
Lesch, Klaus-Peter, Murphy, Dennis L.
Reduction in the Density and
Expression, But Not G-Protein Coupling, of Serotonin Receptors (5-HT1A) in 5-HT
Transporter Knock-Out Mice: Gender and Brain Region Differences
Neurosci. 2000 20: 7888-7895 [Full
Bosker FJ, Klompmakers A, Westenberg HG
Postsynaptic 5-HT1A receptors mediate 5-hydroxytryptamine release in the amygdala
through a feedback to the caudal linear raphe.
Eur J Pharmacol
1997 Aug 27;333(2-3):147-57 [Abstract]
Serotonin modulates N- and P-type
calcium currents in neocortical pyramidal neurons via a membrane-delimited pathway.
J Neurophysiol 1996 Feb;75(2):648-59
"The 5HT modulation
was mimicked by 5HT1A agonists and was reduced by 5HT1A antagonists. 5HT2 antagonists
had no effect on the modulation. These data suggest that the 5HT effects were
mediated by 5HT1A receptors." [Abstract]
Guido, Marcoli, Manuela, Pepicelli, Olimpia, Rosu, Christian, Viola, Concetta,
Serotonin inhibition of the NMDA receptor/nitric
oxide/cyclic GMP pathway in human neocortex slices: involvement of 5-HT2C and
Br. J. Pharmacol. 2000 130: 1853-1858
Testa R, Guarneri L, Angelico P, Velasco C, Poggesi E, Cilia
A, Leonardi A.
Effect of different 5-hydroxytryptamine receptor
subtype antagonists on the micturition reflex in rats.
BJU Int 2001 Feb;87(3):256-64
"These findings confirm that only selective
5-HT1A receptor antagonists have favourable effects on the bladder, inducing an
increase in bladder capacity with no derangement of bladder contractility."
F., Boulenguez, P., Semont, A., Hery, M., Pesce, G., Becquet, D., Faudon, M.,
Deprez, P., Fache, M.-P.
Identification and Role of Serotonin 5-HT1A
and 5-HT1B Receptors in Primary Cultures of Rat Embryonic Rostral Raphe Nucleus
J Neurochem 1999 72: 1791-1801 [Abstract]
Li, Q., Muma, N. A., Battaglia, G., Van
De Kar, L. D.
A Desensitization of Hypothalamic 5-HT1A Receptors
by Repeated Injections of Paroxetine: Reduction in the Levels of Gi and Go Proteins
and Neuroendocrine Responses, but Not in the Density of 5-HT1A Receptors
J Pharmacol Exp Ther 1997 282: 1581-1590 [Full
Raap, D. K., Evans, S., Garcia, F., Li,
Q., Muma, N. A., Wolf, W. A., Battaglia, G., Van De Kar, L. D.
Injections of Fluoxetine Induce Dose-Dependent Desensitization of Hypothalamic
5-HT1A Receptors: Reductions in Neuroendocrine Responses to 8-OH-DPAT and in Levels
of Gz and Gi Proteins
J Pharmacol Exp Ther 1999 288: 98-106
Griebel G, Rodgers RJ, Perrault G, Sanger DJ.
assessment behaviour: evaluation of utility in the study of 5-HT-related drugs
in the rat elevated plus-maze test.
Pharmacol Biochem Behav
"The present findings demonstrate that risk assessment
responses are sensitive to the action of 5-HT1A receptor ligands, but their modulation
by drugs targetting 5-HT2A, 5-HT2C, and 5-HT3 receptors was not convincingly established."
Browning, Kirsteen N., Travagli, R. Alberto
The peptide TRH uncovers the presence of presynaptic 5-HT1A receptors via activation
of a second messenger pathway in the rat dorsal vagal complex
Physiol (Lond) 2001 531: 425-435 [Full