Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the distribution of [3H]5-carboxamidotryptamine ([3H]5-CT) binding sites by in vitro autoradiography on sections of guinea-pig and rat brain. In saturation studies, the ligand recognised a saturable, homogeneous population of binding sites with an affinity ranging from 0.19-0.45 nM depending on the region. The labelling pattern was heterogeneous, and the displacement pattern with different competing drugs selective for different 5-HT receptor subtypes was complex. [3H]5-CT appeared to label 5-HT1B/5-HT1D sites in the substantia nigra, globus pallidus and caudate/putamen, as the binding in these regions was displaced by the 5-HT1B/1D receptor selective agents sumatriptan, CP-122,288 and GR-127,935. In the hippocampus and lateral septum, the very dense [3H]5-CT binding was displaced with high affinity by the 5-HT1A receptor selective agonist 8-hydroxy-dipropylaminotetralin ((+/-)-8-OH-DPAT), dihydroergotamine and 5-HT. In contrast the affinity of the 5-HT1 receptor antagonists spiperone and methiothepine was much lower than their previously published potency at 5-HT1A receptors. The affinity of agonists, taken together with the fact that the distribution of these [3H]5-CT sites overlaps that of [3H]8-OH-DPAT binding sites in serial sections, suggest that these sites correspond to 5-HT1A receptors. Their atypical properties deserve further investigations. While [3H]5-CT binding at 5-HT1B/1D sites and these atypical 5-HT1A sites was inhibited by the GTP analogue 5'-beta, gamma-imidotriphosphate, [3H]5-CT binding in the superficial cortical layers and in midline thalamic nuclei was insensitive to this agent. It was however displaced by low concentrations of spiperone, clozapine and methiothepine, but not by sumatriptan, CP-122,288, GR-127,935 or dihydroergotamine. This binding profile is similar to that of 5-HT7 receptors, while the spatial distribution of these sites matches the known distribution of 5-HT7 messenger RNA. We did not find evidence of [3H]5-CT labelling to 5-HT5 receptors, in spite of their reported high affinity for this ligand. It is concluded that [3H]5-CT, in the presence of selective blockers, can be used to investigate the properties of 5-HT1A, 5-HT1B/1D and 5-HT7 receptors in the rodent brain, although further studies are required to explain the atypical features of [3H]5-CT binding in 5-HT1A receptors containing regions.
Eur J Pharmacol 1995 Sep 05
PMID:Autoradiographic visualisation of [3H]5-carboxamidotryptamine binding sites in the guinea pig and rat brain. 749 19

Groups of rats were treated with buspirone (1 mg/kg/day) for 21 days using osmotic minipumps implanted subcutaneously. After buspirone treatment, the 5-HT1A receptor mRNA levels were significantly decreased in the CA1 and CA2 of the hippocampus, but were markedly increased in the dentate gyrus (DG), CA3 and CA4. The level of the 5-HT1A receptor binding sites was not significantly changed in these subhippocampal areas. Buspirone treatment markedly increased 5-HT2A receptor mRNA levels in the DG, CA2, CA3 and CA4. This was accompanied by a significant increase in the level of 5-HT2A receptor binding sites in all subhippocampal regions. These results demonstrate that chronic buspirone treatment differentially regulates 5-HT1A and 5-HT2A receptor mRNA as well as their expressed binding sites in various regions of the hippocampus.
Brain Res Mol Brain Res 1995 Sep
PMID:Chronic buspirone treatment differentially regulates 5-HT1A and 5-HT2A receptor mRNA and binding sites in various regions of the rat hippocampus. 750 Aug 48

To explore the role of 5-HT receptor subtypes in controlling aversion, we measured the effect of 5-HT1A and 5-HT2A/2C receptor agonists microinjected into the dorsal periaqueductal gray (DPAG) of rats on aversive behavior induced by electrical stimulation of the same brain area. The 5-HT1A agonists 8-OH-DPAT (4-16 nmol) and BAY-R-1531 (4-16 nmol) raised the threshold of aversive electrical stimulation in a dose-dependent way. Similarly, microinjection of the 5-HT2A/2C agonist DOI (4-16 nmol) increased the aversive mCPP (16 and 32 nmol) was ineffective. Previous intra-DPAG administration of the 5-HT1A receptor blocker NAN-190 (40 nmol) antagonized the antiaversive effect of 8-OH-DPAT (8 nmol), whereas pretreatment with the 5-HT2A receptor blocker spiperone (10 nmol) antagonized the effect of DOI (16 nmol). Spiperone also counteracted the effect of 8-OH-DPAT and NAN-190 counteracted the effect of DOI. These results indicate that activation of 5-HT1A and 5-HT2A receptors inhibits aversion in the DPAG and that both receptors have to be functional for the expression of each one's activation to occur.
Pharmacol Biochem Behav 1995 Sep
PMID:Role of 5-HT receptor subtypes in the modulation of dorsal periaqueductal gray generated aversion. 750 49

The effects of different housing conditions and ethanol treatment (6 vol % in the drinking water) on the in vitro binding characteristics of striatal dopaminergic D2 ([3H]spiperone), hippocampal serotonergic 5-HT1A ([3H]8-OH-DPAT), and cortical benzodiazepine ([3H]flunitrazepam) receptors have been examined. Social deprivation due to contact caging, short- (1 day) and long-term isolation (5 weeks) yielded a significant decrease of striatal D2 receptor density with the greatest decrease after long-term isolation (-21% Bmax) without changes of Kd in comparison to group animals. The effect of ethanol on striatal D2 receptor density depended on the housing conditions. Whereas ethanol treatment reduced receptor density of group animals (down to 88%), chronic exposure to ethanol under long-term isolation elicited no significant alteration of D2 receptor density compared with group animals. Different housing and ethanol treatment had no effect on 5-HT1A receptor affinity and density. Alterations of benzodiazepine receptor density were not found, but social deprivation as well as ethanol treatment of group animals caused an increased affinity of [3H]flunitrazepam (reduced Kd value). These results indicate that different housing conditions of adult rats evoked significant alterations in D2 and benzodiazepine receptor binding assays, which were modified by ethanol treatment in the case of striatal D2 receptor density.
Pharmacol Biochem Behav 1995 Sep
PMID:Influences of housing conditions and ethanol intake on binding characteristics of D2, 5-HT1A, and benzodiazepine receptors of rats. 750 70

The selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) reduces the activity of brain 5-HT neurons via somatodendritic autoreceptors located in the midbrain raphe nuclei. This action of 8-OH-DPAT results in reduced 5-HT synthesis and release of 5-HT in terminal regions. Previous studies have shown that injecting 8-OH-DPAT into the raphe nuclei stimulates feeding, sexual behaviour, and locomotor activity, and serves as an unconditioned stimulus for inducing a conditioned place preference. This behavioural profile suggests that raphe injections of 8-OH-DPAT facilitate reward-related behaviour. The present study tested this hypothesis by investigating the effects of median raphe injections of 8-OH-DPAT on sensitivity to lateral hypothalamic (LH) self-stimulation. Frequencies required to sustain half-maximal rates of responding were determined following injection of saline or various doses of 8-OH-DPAT (0.2-5 micrograms) into the median raphe. In four rats with accurate injection sites 8-OH-DPAT dose-dependently lowered frequency thresholds by up to 40%. In the remaining rats injection sites were located outside the median raphe, and 8-OH-DPAT either slightly raised or failed to lower frequency thresholds. These results show that 8-OH-DPAT injected into the median raphe facilitates brain stimulation reward, and suggest that acute reductions in 5-HT neurotransmission may enhance sensitivity to rewarding stimuli. The possible interactions between 5-HT neurons and efferent systems utilizing dopamine and acetylcholine as neurotransmitters in mediating this effect are discussed.
Pharmacol Biochem Behav 1995 Sep
PMID:Median raphe injections of 8-OH-DPAT lower frequency thresholds for lateral hypothalamic self-stimulation. 750 80

Although it has been previously proposed that 5-HT1B agonism specifically attenuates rodent agonistic behaviour, more recent investigations have indicated that such influences may be ancillary to an anxiogenic effect. The present study examined the influences of two 5-HT1B agonists, CGS 12066B and CP-94,253, on murine agonistic behaviour. In a resident-intruder paradigm, CGS 12066B (0.5-5.0 mg/kg) decreased resident offensive aggression, social interest, and exploration while dose-dependently enhancing defensive behaviours across the dose range tested. CP-94,253 (2.5-10.0 mg/kg) also reduced elements of resident offensive behaviour whereas defensive behaviours were largely unchanged. Some elements of resident nonsocial and social behaviour were enhanced at 2.5 and 5.0 mg/kg but decreased at 10.0 mg/kg. The behavioural profile of CP-94,253, but not CGS 12066B, supports the proposal that 5-HT1B receptors inhibit agonistic behaviour without concomitant sedative or anxiogenic effects. Findings are discussed in relation to 5-HT1A/1B/2C receptors involved in agonistic behaviour and anxiety.
Pharmacol Biochem Behav 1995 Sep
PMID:Differential effects of CGS 12066B and CP-94,253 on murine social and agonistic behaviour. 750 81

(-)-LY293284, (-)-4R-6-acetyl-4-(di-n-propylamino)1,3,4,5- tetrahydrobenz[c,d]indole, is a conformationally restricted tryptamine derivative with an acetyl group serving as a protophilic substitution for the hydroxyl in serotonin (5-HT). In ligand displacement studies, LY293284 had a Ki of 0.07 nM for the 5-HT1A receptor but no affinity for other monoaminergic receptors within 3 orders of magnitude. LY293284 was evaluated in in vivo models, which have been used as markers for presynaptic and postsynaptic 5-HT1A receptor activity. LY293284 decreased hypothalamic 5-hydroxyindoleacetic acid levels (ED50, 2.9 micrograms/kg s.c.) and dorsal raphe serotonergic neuron firing rate (ED50, 0.08 micrograms/kg s.c.), which are accepted indices of presynaptic activity. LY293284 also induced a reduction in body temperature in rats (ED50, 3.6 micrograms/kg s.c.), which was blocked by pretreatment with (+/-)-pindolol. Hypothermic responses of rats to 5-HT1A agonists have had both pre- and postsynaptic characteristics in previous studies. The ED50 values for 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) in these tests were 15 to 45 times higher than those observed for LY293284. In models for postsynaptic activity, the ED50 for LY293284 for elevating serum corticosterone levels was 9.7 micrograms/kg s.c. and the minimum effective doses to induce lower lip retraction and flat posture were 3 micrograms/kg s.c. For comparison, the same indices obtained for 8-OH-DPAT were 222.4 and 100 micrograms/kg, respectively. The 5-HT syndrome responses induced by LY293284 were also attenuated by pretreatment with (+/-)-pindolol. LY293284 was 10 times more potent than 8-OH-DPAT in a drug discrimination test that used pigeons trained to identify 8-OH-DPAT. In sexual behavior tests with male rats, LY293284 induced a maximal reduction in ejaculatory latency at 0.01 micrograms/kg s.c., which was approximately 10 times higher potency than 8-OH-DPAT. In the pigeon conflict model for anxiolytic activity, LY293284 was 100 times more potent than 8-OH-DPAT in increasing punished responding. In the rat forced swim model for antidepressant-like activity, LY293284 was 30 and 35 times more potent than 8-OH-DPAT in decreasing immobility time and defecation rate. These studies have demonstrated that LY293284 is a highly selective and extremely potent 5-HT1A receptor agonist and represents a useful pharmacological tool for studying 5-HT1A receptor-mediated effects.
J Pharmacol Exp Ther 1994 Sep
PMID:Pharmacological characterization of LY293284: A 5-HT1A receptor agonist with high potency and selectivity. 752 57

The vascular effects of serotonin (5-hydroxytryptamine, 5-HT) are complex and heterogeneous. In human forearm, we showed that low doses of 5-HT cause marked but transient vasodilatation followed by a persistent vasodilator response. In in vitro and in animal experiments, 5-HT induced release of nitric oxide (NO) through stimulation of endothelial 5-HT1-like receptors. In the present study, we investigated involvement of the "NO pathway" and possible involvement of the 5-HT1A receptor subtype in 5-HT-induced persistent vasodilator response. In 8 healthy volunteers, we infused 5-HT (0.1, 0.3, and 1 ng/kg/min) and the selective 5-HT1A receptor agonist flesinoxan (15, 45, and 150 ng/kg/min) intraarterially (i.a.) with NG-monomethyl-L-arginine (L-NMMA 30 micrograms/kg/min) or saline. Forearm blood flow (FBF) was measured by automated R-wave-triggered venous occlusion plethysmography. Forearm vascular resistance (FVR) was derived from simultaneously recorded i.a. blood pressure (BP) and FBF. 5-HT dose-dependently decreased FVR (p < 0.001). The persistent vasodilator response to 5-HT appears to be mediated by NO release, as suggested by its complete abolition by L-NMMA (p < 0.001). Flesinoxan decreased FVR slightly, but only at high doses (p < 0.05). The present findings indicate that 5-HT1A receptors are not functionally involved in 5-HT-mediated vasodilatation in human forearm.
J Cardiovasc Pharmacol 1994 Sep
PMID:No functional involvement of 5-hydroxytryptamine1A receptors in nitric oxide-dependent dilatation caused by serotonin in the human forearm vascular bed. 752 2

Serotonin (5-hydroxytryptamine, 5-HT) receptors as well as dopamine receptors are important in connection with schizophrenia. In this study we evaluated the effects of the 5-HT1A receptor agonist (8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT) and 5-HT1B receptor agonist (1-(3-trifluoromethylphenyl)piperazine, TFMPP) on the single and paired rats' movement distance in an open-field. Generally animals are gregarious in their natural setting, so the presence of another companion might alter the effects of the drugs. Therefore we devised a video analysis system to pick up the two rats' movements individually through two CCD video cameras and objectively recorded two rats' movement for 30 minutes. Experimental rats were injected with 8-OH-DPAT (0.05, 0.25, 1.25, 6.25 mg/kg, s.c.) or TFMPP (0.12, 0.5, 2.0, 8.0 mg/kg, i.p.) and the control rats were injected with saline. In the single cases experiments, the rats were put alone into the open field after the injection. In the paired cases experiments, they were put into the open field with a companion rat after the injection. In the 8-OH-DPAT experiment, the movement distance of single cases showed dose dependent increase tendency and that of the 1.25 mg/kg group and the 6.25 mg/kg group showed significant increase, but that of paired cases did not show that tendency, on the contrary, the movement distance of 0.05 mg/kg group showed significant decrease. In the TFMPP experiment, the movement distance of 2.0 mg/kg groups showed significant increases in the single and the paired cases. These findings suggest that both 5-HT1A receptors and 5-HT1B receptors affect the rats' movement distance.(ABSTRACT TRUNCATED AT 250 WORDS)
No To Shinkei 1995 Sep
PMID:[Effects of 5-HT1A receptor agonist and 5-HT1B receptor agonist on single and paired rats' behavior]. 754 36

The human 5-HT1A receptor was expressed in Sf9 insect cells to examine desensitization as manifested by agonist-induced uncoupling from G proteins and second messengers. New binding sites were detected after infection of cells with the 5-HT1A receptor-bearing baculovirus. 5-HT1A receptor agonists caused inhibition of cAMP accumulation that could be attenuated by specific receptor antagonists. Brief pretreatment with 5-HT resulted in (1) an uncoupling of receptor from G proteins as evidenced by a loss of high-affinity agonist binding sites and a diminished ability of the receptor to increase incorporation of AA-GTP into endogenous Go alpha-like G proteins, (2) a decreased ability of the receptor to inhibit cAMP accumulation, and (3) increased phosphorylation of the 5-HT1A receptor on serine and threonine residues. Phosphorylation occurred in the presence of a number of cyclic nucleotide dependent kinase inhibitors, and desensitization of the cAMP response occurred in the presence of H-7 and also in cells with prolonged exposure to PMA. Both phosphorylation and desensitization were markedly attenuated by 100 nM and 1 microM heparin and demonstrated similar time courses and concentration-response relationships. Those results demonstrate a close association between agonist-induced desensitization and phosphorylation of the 5-HT1A receptor in Sf9 cells through a pathway that mainly does not involve protein kinase A or C and might involve a G protein-linked receptor kinase.
Biochemistry 1995 Sep 19
PMID:Agonist-induced desensitization and phosphorylation of human 5-HT1A receptor expressed in Sf9 insect cells. 754 32


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