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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four major families of serotonin (5-hydroxytryptamine; 5-HT) receptors have been identified: 5-HT1, 5-HT2, 5-HT3 and 5-HT4. At this time, there is a general consensus that the 5-HT1 family can be further subdivided into 5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, and 5-HT1P subpopulations. In addition, there are several other populations of less well-defined 5-HT receptors. The purpose of this presentation is to discuss 5-HT receptor nomenclature and the agents that are commonly used to investigate each receptor population in as much as it will serve to provide background for the remainder of the symposium. There is presently available an abundance of serotonergic agents; however, these agents are only semiselective, and none can be considered truly selective for a particular population of 5-HT receptors. As useful as these agents have been for the identification and characterization of 5-HT receptors, there remains a need for the development of new, more selective ligands.
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PMID:Serotonin receptors and their ligands: a lack of selective agents. 181 55

The recent cloning of three types of 5-hydroxytryptamine (5-HT, serotonin) receptors substantiates radioligand-based definitions of 5-HT receptors, and provides a framework in which to understand the function and evolution of the receptors. The primary sequences determined by molecular cloning of the 5-HT1c, 5-HT1a and 5-HT2 receptors place each of these 5-HT receptor subtypes into the class of G protein-coupled receptors. These receptors all share similar functional and structural features. Each receptor is positioned in the lipid bilayer with seven membrane-spanning domains and corresponding intracellular and extracellular domains. By analogy to the known functional structures of the beta-adrenergic receptor, the binding site of 5-HT is proposed to be in the membrane domains and the intracellular domain is important for G protein interaction. The primary sequences and the second messenger systems of the receptors indicate the 5-HT2 and 5-HT1c receptors are closely related, whereas the 5-HT1a receptor is more distantly related to the 5-HT2 and 5-HT1c receptors.
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PMID:Molecular biology of serotonin (5-HT) receptors. 181 59

The 5-hydroxytryptamine (5-HT) receptor by which 5-HT can evoke nonadrenergic noncholinergic (NANC) relaxations in isolated guinea-pig proximal colon was characterized using a variety of 5-HT receptor agonists and antagonists. In the presence of atropine (0.2 microM), guanethidine (5 microM) and ketanserin (10 microM), a concentration-dependent relaxation was obtained with 5-HT (apparent mean pEC50 value 6.43), 5-CT (5.64) and 5-CH3-T (5.02); 8-OH-DPAT, TFMPP, GR43175 and 5-OCH3-N,N-DMT (up to 100 microM) did not relax the guinea-pig proximal colon. The nonselective 5-HT receptor antagonist, metitepine (0.1 microM), the 5-HT1C/5-HT2 receptor antagonists, mianserin (1 microM) and pizotifen (0.1 microM), and the 5-HT1A/5-HT2 receptor antagonists spiperone (3 microM) shifted the concentration-response curves for 5-HT to the right. The 5-HT1A/5-HT1B receptor antagonist, cyanopindolol (0.3 microM) and a selective 5-HT3 receptor antagonist, ICS205-930 (1 microM) failed to block the 5-HT-induced NANC relaxation. In conclusion, the experiments with agonists and antagonists are compatible with the view that a 5-HT1-like receptor is involved in 5-HT-induced NANC relaxations of the guinea-pig proximal colon.
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PMID:Characterization of 5-hydroxytryptamine-induced relaxations of guinea-pig proximal colon. 181 62

The selective 5-hydroxytryptamine (5-HT1A) receptor agonist 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) induces a large number of pharmacological effects. In the present study we demonstrate that a novel 8-OH-DPAT analog, (S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin [(S)-UH-301], is able to antagonize completely the following (R)-8-OH-DPAT-induced effects in the rat: 1) reduction in brain 5-HT biosynthesis, measured as a decreased 5-hydroxytryptophan-accumulation after decarboxylase inhibition; 2) induction of the 5-HT1A behavior (flat body posture, forepaw treading and hindlimb abduction) in reserpine-pretreated animals; 3) reduction of body temperature; 4) inhibition of the cage-leaving response; and 5) reduction of 5-hydroxytryptophan- and quipazine-induced wet dog shakes. In addition, (S)-UH-301 reverses the 5-HT-induced inhibition of the forskolin stimulated cyclic AMP production in rat hippocampus without producing any effects per se in this assay. It is shown that high doses of (S)-UH-301 decrease rat brain biosynthesis of dopamine. These and previous data indicate that (S)-UH-301 also is a weakly potent dopamine-receptor agonist, but with a lower affinity for D2 as compared to 5-HT1A receptors. Thus, the data suggest that (S)-UH-301 is a 5-HT1A-receptor antagonist without intrinsic activity. Therefore, it is likely that (S)-UH-301 will become a valuable pharmacological tool in future 5-HT research.
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PMID:Pharmacology of the novel 5-hydroxytryptamine1A receptor antagonist (S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin: inhibition of (R)-8-hydroxy-2-(dipropylamino)tetralin-induced effects. 183 99

1. Acetylcholine (ACh) release from the cerebral cortex of freely moving guinea-pigs, implanted with epidural cups, was studied. 2. A single dose of chlorimipramine (Cl-Imip, 10 mg kg-1, s.c.), reduced the cortical ACh release both in normal and in chronically (10 mg kg-1 daily, s.c., for 14 days) Cl-Imip-treated guinea-pigs; the 5-HT3 antagonist MDL 72222 (1 mg kg-1, s.c.) antagonized this effect. 3. A single dose of Cl-Imip significantly reduced the effect of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylaminotetralin) (8-OH-DPAT, 0.1 mg kg-1, s.c.), which nearly doubled the cortical ACh release in control animals. MDL 72222 restored to normal the response to 8-OH-DPAT reduced by the anti-depressant. 4. A single dose of Cl-Imip did not change the inhibitory, MDL 72222-sensitive, effect induced by the 5-HT3 agonist 2-methyl-5-hydroxytryptamine (2-methyl-5-HT, 500 micrograms, i.c.v.). 5. In chronically Cl-Imip-treated guinea-pigs, the facilitatory effect of 8-OH-DPAT was no longer present, while the inhibitory, MDL 72222-sensitive, effect of 2-methyl-5-HT was maintained. 6. These results indicate that the 5-HT1A receptor-mediated increase in ACh release is reduced by prolonged Cl-Imip treatment, while the 5-HT3 receptor-mediated inhibition of ACh release is unaffected. The relevance of these findings to the antidepressant mechanism of Cl-Imip is discussed.
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PMID:Influence of acute and chronic chlorimipramine treatment on the 5-HT receptor-mediated modulation of acetylcholine release from the cerebral cortex of freely moving guinea-pigs. 183 Feb 35

The effects of 5-hydroxytryptamine (5-HT) and of a number of 5-HT receptor agonists and antagonists on the release of endogenous aspartate were investigated in rat cerebellum slices and synaptosomes depolarized with high K+. The release of endogenous aspartate evoked from slices by 35 mmol/l KCl and from synaptosomes by 15 mmol/l KCl was strongly (about 90%) calcium-dependent. In slices the release of aspartate was inhibited by exogenous 5-HT (0.1-100 nmol/l) in a concentration-dependent manner. The indoleamine was very potent, producing 30% inhibition at 0.1 nmol/l. The effect of 10 nmol/l 5-HT was partly but maximally counteracted by ketanserin (300-1000 nmol/l), a 5-HT2 receptor antagonist, but fully blocked by 300 nmol/l of the mixed 5-HT1/5-HT2 receptor antagonist methiothepin. The 5-HT1A receptor agonist 5-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) inhibited the K(+)-evoked release of endogenous aspartate in a concentration-dependent manner. The effect of 8-OH-DPAT was antagonized by methiothepin, but not by ketanserin which fully antagonized the inhibition produced by DOI. In cerebellar synaptosomes the release of endogenous aspartate evoked by 15 mmol/l K+ was inhibited by exogenous 5-HT and by 8-OH-DPAT, but not by DOI. Methiothepin (100-300 nmol/l) antagonized the inhibitory effects of 100 nmol/l 5-HT or 8-OH-DPAT. However, 1000 nmol/l of various 5-HT receptor antagonists [ketanserin, methysergide, (--)-propranolol, spiperone or ICS 205-930] did not counteract the effect of 100 nmol/l 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Release of endogenous aspartate from rat cerebellum slices and synaptosomes: inhibition mediated by a 5-HT2 receptor and by a 5-HT1 receptor of a possibly novel subtype. 183 Sep 29

1. The motor behavioural effects of intrathecal injections of 5-hydroxytryptamine (5-HT) and a variety of 5-HT receptor agonists were examined in adult Wistar rats to establish; (a) which 5-HT receptor subtype/s elicit each behaviour and (b) whether these receptors are located within the spinal cord. 2. Intrathecal injection of 5-methoxy-N,N'-dimethyltryptamine (5-MeODMT), (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) or 2,5-dimethoxy-alpha,4-dimethylbenzene ethamine hydrochloride (DOM) produced dose-related back muscle contractions (BMC) and wet dog shakes (WDS) which were both markedly attenuated by intraperitoneal pretreatment with either ritanserin (1 mg kg-1), ketanserin (0.16 mg kg-1) or mianserin (0.6 mg kg-1) indicating the involvement of 5-HT2 receptors in both these motor behaviours. Both fluoxetine (1-20 mg kg-1, i.p.) and high doses of 5-HT (50 micrograms) following fluoxetine (5 mg kg-1, i.p.) also elicited BMC, further confirming the involvement of 5-HT in this behaviour. 3. Intrathecal 5-carboxamidotryptamine (5-CT) evoked a marked wet-dog shake response without producing any BMC. Intrathecal pretreatment with 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) enhanced, while in contrast 2-methyl-5-HT pretreatment attenuated, 5-HT agonist-induced BMC without affecting WDS. These data suggest that the spinal 5-HT2 receptors mediating BMC are positively modulated by 5-HT1A but negatively influenced by 5-HT3 receptor activation and may be of a different subtype to the supra-spinal 5-HT2 receptors which elicit WDS. 4. A contrast, reciprocal forepaw treading, lateral head weaving, flat body posture and Straub-tail were evoked by 5-MeODMT, 8-OH-DPAT or 5-CT but not by DOI or DOM indicating that these behaviours were not produced by 5-HT2 receptor activation alone. Ritanserin (1 mg kg- 1, i.p.) or ketanserin (0.16mgkg-1, i.p.) pretreatment reduced the reciprocal forepaw treading induced by high intrathecal doses of either 5-MeODMT (25.pg) or 5-CT (50,ug) suggesting that this behaviour may be facilitated by 5-HT2 receptor activation. 5. Intrathecal injection of 5-HT (0.05-50pg, after systemic fluoxetine, 5mg kg 1, i.p.), or 1-(3-chlorophenyl) piperazine (mCPP) produced dose-related forepaw-licking and grooming, neither of which were attenuated by ketanserin (0.16 mgkg-1, i.p.) pretreatment suggesting these behaviours may be mediated by 5-HT1c receptors. In contrast, 2-methyl-5-HT (50 and 100pg) produced sideward tail-flicks, not evoked by any other 5-HT agonist and could therefore be mediated by spinal 5-HT3 receptor activation. 6. These data provide behavioural evidence for the existence of spinal 5-HT2 receptors which produce a novel motor behaviour, BMC. Ligand binding studies and dose-response studies with a range of selective 5-HT antagonists are required to establish whether BMC and WDS are mediated by different subtypes of 5-HT2 receptors.
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PMID:Characterization of the 5-HT receptor subtypes involved in the motor behaviours produced by intrathecal administration of 5-HT agonists in rats. 183 68

1. Parallel series of experiments were carried out in the rat and mouse in order to investigate the mechanism(s) underlying the hypothermia induced in rodents by the selective 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). 2. In the mouse, lesioning of central 5-hydroxytryptaminergic neurones (by use of the neurotoxin, 5,7-dihydroxytryptamine; 5,7-DHT) abolished the hypothermic response to 8-OH-DPAT, and depletion of brain 5-hydroxytryptamine (5-HT) levels (with the 5-HT synthesis inhibitor, p-chlorophenylalanine) markedly attenuated the response in this species. These pretreatments did not significantly attenuate 8-OH-DPAT-induced hypothermia in the rat, except for a significant attenuation of the response in 5,7-DHT-lesioned rats at the top dose of 8-OH-DPAT (1.0 mg kg-1, s.c.). 3. Pharmacological pretreatments which facilitate 5-HT release (selective 5-HT uptake inhibitors, precursor (5-hydroxytryptophan) loading, or fenfluramine), markedly attenuated or abolished 8-OH-DPAT-induced hypothermia in the mouse. These pretreatments generally had no significant effect on 8-OH-DPAT-induced hypothermia in the rat. 4. The selective noradrenaline uptake inhibitor, desipramine, had no effect on the hypothermic response to 8-OH-DPAT in either species. The selective dopamine uptake inhibitor, nomifensin, significantly increased the hypothermic response to 8-OH-DPAT in the mouse, but did not affect the response in the rat except at high, motor stimulant doses, when the response was attenuated. 5. These data are consistent with the hypothesis that 8-OH-DPAT-induced hypothermia is mediated by presynaptic autoreceptors in the mouse and by postsynaptic 5-HT1A receptors in the rat. Preliminary data also indicate an involvement of dopamine release in the mouse but not in the rat.
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PMID:Direct evidence for an important species difference in the mechanism of 8-OH-DPAT-induced hypothermia. 183 17

The potencies of 5-methoxy-N, N-dimethyltryptamine (central 5-hydroxytryptamine 1 receptor agonist) and 8-hydroxy-2-(di-n-propylamino) tetralin (central 5-hydroxytryptamine 1A receptor agonist) in eliciting head-weaving behaviour were studied in streptozotocin-diabetic mice and a group of control animals. Both drugs induced head-weaving behaviour in the streptozotocin-diabetic mice and control animals, but the potencies of these 5-hydroxytryptamine 1 agonists were reduced in the streptozotocin-diabetic mice. The numbers of head weaves elicited in the streptozotocin-diabetic and control animals by the two drugs were suppressed by pre-treatment with propranolol (5-hydroxytryptamine 1A receptor antagonist) and methysergide (5-hydroxytryptamine 1 and 2 receptor antagonist), but not by ketanserin (5-hydroxytryptamine 2 receptor antagonist), confirming the involvement of the 5-HT1A receptor. Pretreatment with nicotinamide before administering streptozotocin prevented streptozotocin-induced hyperglycaemia and restored the inhibition of head-weaving behaviour observed in streptozotocin-diabetic mice. Insulin injection, which partially prevented streptozotocin-induced hyperglycaemia, completely prevented reduction of the number of head weaves elicited by 5-methoxy-N, N-dimethyltryptamine in streptozotocin-diabetic mice. These results suggest that the reduced response to 5-HT1 agonists in streptozotocin-diabetic mice may be caused by the depletion of insulin.
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PMID:Effects of two 5-hydroxytryptamine agonists on head-weaving behaviour in streptozotocin-diabetic mice. 183 8

Rats were reared from weaning (21 days of age) either in isolation or in social groups of five for 30 days and were then tested for spontaneous locomotor activity and 7 days later for 5-hydroxytryptamine (5-HT) agonist-induced behaviour. Isolation-reared animals displayed locomotor hyperactivity when placed in a novel environment. 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) (2 mg/kg IP) and 8-hydroxy-2-(di-n-propyl-amino) tetralin (8-OH-DPAT) (0.32 mg/kg SC) elicited various components of the "5-HT behavioural syndrome" in both groups of animals, with forepaw treading and flat body posture being significantly more pronounced in isolation-reared animals. 1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (2.5 mg/kg IP), a 5-HT2 selective agonist, produced a significantly greater number of back muscle contractions in isolation-reared animals but there was no difference between the two groups in the number of wet-dog shakes produced. Forepaw treading and flat body posture are thought to be mediated by 5-HT1A receptor activation, and stimulation of this receptor by either 5-MeODMT or 8-OH-DPAT produced greater responding in isolation-reared rats, suggesting supersensitivity of the post-synaptic 5-HT1A receptor. Wet-dog shakes are thought to be mediated by 5-HT2 and other (none-5-HT) receptors while back muscle contractions have been shown to be mediated by 5-HT2 receptors, indicating that there is also an increase in 5-HT2 receptor responsiveness in the socially-isolated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of isolation rearing on 5-HT agonist-induced responses in the rat. 183 66


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