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)

The 5-hydroxytryptamine (5-HT) receptor mediating endothelium-dependent relaxation of pig coronary arteries was characterized using a variety of 5-HT receptor agonists and antagonists. Unrubbed (with endothelium preserved) rings precontracted by prostaglandin F2 alpha in the presence of ketanserin relaxed in an endothelium-dependent manner to 5-HT, 5-carboxamidotryptamine and 5-methoxytryptamine with about equal potency and efficacy. By comparison, bufotenine, 3-(dimethylamino)ethyl-N-methyl-1H-indole-5-methane sulfonamide, (-)-alpha-methyl-5-HT,N,N-dipropyl-5-carboxamidotryptamine and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H indole were half-efficient and other drugs [in particular the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin] were inactive as agonists up to 0.1 mM. The effect of 5-carboxamidotryptamine was antagonized in an apparently competitive manner by 15 drugs. Among the most potent antagonists (mean pKB value) were the nonselective 5-HT receptor antagonists, methiothepin (7.30) and metergoline (6.86), the 5-HT1A/5-HT1D receptor ligand, 1-[2-(4-amino-phenyl)ethyl]-4-(3-trifluoromethylphenyl)-piperazine (7.02), the 5-HT1A/5-HT1B/5-HT1D receptor ligand, 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrrolo[1,2,-a]quinoxaline 1 (6.73) and yohimbine (6.37). Selective ligands for 5-HT1A receptors were either inactive [8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide] or poorly active (spiperone, 4.44). Beta-adrenoceptor antagonists with affinity for 5-HT1A and 5-HT1B receptors weakly antagonized the effect of 5-carboxamidotryptamine (pKB values less than or equal to 5.32), as did the 5-HT1c/5-HT2 receptor antagonist, mesulergine (5.30) and the yohimbine isomer, corynanthine (4.85). Methysergide was clearly a noncompetitive antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:5-Hydroxytryptamine (5-HT)-induced endothelium-dependent relaxation of pig coronary arteries is mediated by 5-HT receptors similar to the 5-HT1D receptor subtype. 213 76

The purpose of the present study was to characterize the cardiorespiratory effects of activation of 5-HT1A, 5-HT1B and 5-HT2 receptor subtypes at the intermediate area of the ventral surface of the medulla. The agonists (+/-)-8-hydroxy-2-(di-N-propylamino)tetralin hydrobromide (8-OH-DPAT), 1-[3-(trifluoromethyl)phenyl]-piperazine hydrochloride (TFMPP) and (+/-)-1-(2,5-di-methoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) were used to activate these receptor subtypes, respectively. Application of each drug to the intermediate area produced a different profile of cardiorespiratory effects. 8-OH-DPAT (0.0625-4.0 micrograms) produced dose-dependent hypotension and bradycardia, which were antagonized by the 5-HT1A antagonists spiperone and spiroxatrine. The bradycardia was blocked by bilateral vagotomy. No significant changes in respiratory motor outflow to the larynx or diaphragm were observed after application of 8-OH-DPAT. TFMPP (10-1000 micrograms) also produced a dose-dependent hypotension and bradycardia. However, these effects were not antagonized by spiperone or blocked by vagotomy. A decrease in the amplitude of the recurrent laryngeal and phrenic nerve signals was observed after application of the highest dose of TFMPP. In contrast to the effects of 8-OH-DPAT and TFMPP, DOI (0.3-100 micrograms) produced an increase in blood pressure without any change in heart rate. Recurrent laryngeal and phrenic nerve activities were depressed, as was respiratory rate, after application of DOI. Both the cardiovascular and respiratory effects of DOI were blocked by the 5-HT2 antagonist ketanserin. These results indicate that activation of ventral medullary 5-HT receptor subtypes produces unique effects on cardiorespiratory activity.
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PMID:Characterization of the effects of activation of ventral medullary serotonin receptor subtypes on cardiovascular activity and respiratory motor outflow to the diaphragm and larynx. 213 22

Behavioral syndromes mediated by serotonergic mechanisms may reflect interactions between distinct effects initiated by specific 5-HT receptors, such as the 5-HT1A and the 5-HT2 receptor. This hypothesis was tested by examining the effect of various 5-HT1A agonists on the 5-HT2 receptor-mediated quipazine-induced head shake response in rats. Subcutaneous administration of 8-OH-DPAT, buspirone, gepirone, and ipsapirone produced a dose-dependent inhibition of the ketanserin-sensitive quipazine-induced head shake response. These effects were produced by doses of agonists which did not induce reciprocal forepaw treading. Furthermore, pretreatment with a partial 5-HT1A agonist (+/-)pindolol blocked the inhibitory effects of 8-OH-DPAT to the level of inhibition produced by (+/-)pindolol itself. These results suggest that stimulation of central 5-HT1A receptors can modulate the expression of a central 5-HT2 receptor-mediated behavior.
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PMID:8-OH-DPAT and buspirone analogs inhibit the ketanserin-sensitive quipazine-induced head shake response in rats. 213 31

Affinities of drugs for 21 indolealkylamine derivatives, some with putative hallucinogenic activity, were determined at 5-HT1A, 5-HT2A and 5-HT2B recognition sites, using radioligand competition studies. Nearly all of the derivatives displayed greatest potency for the 5-HT2A receptor, labelled by [125I]R-(-)DOI in the cortex of the rat. Most derivatives displayed 2-10 times lower affinity at the HT2B receptor labelled by [3H]ketanserin in bovine cortex. Derivatives lacking ring substituents displayed lower affinities for all of the recognition sites, compared to derivatives substituted in the 4- or 5-position of the indole ring. The 4-hydroxylated derivatives displayed 25-380-fold selectivity for the 5-HT2A site, vs the 5-HT1A site, while the 5-substituted derivatives displayed approximately equal potency at the 5-HT1A and 5-HT2A sites. Affinity of all the compounds at the 5-HT2B site was greater than 300 nM. The 6-substituted derivatives displayed greater than micromolar affinities for all of the 5-HT recognition sites examined. The size of the N,N-dialkyl substituent was a secondary determinant of affinity, with groups larger than N,N-diisopropyl resulting in a marked reduction in affinity at both the 5-HT2A and 5-HT1A recognition sites. This study demonstrated that hallucinogenic 4-hydroxy-indolealkylamines, like psychotomimetic phenylisopropylamines, bind potently and selectively to the 5-HT2A recognition site, labelled by [125I]R-(-)DOI. This provides further evidence indicating that this recently described subtype of the 5-HT2 receptor may partially mediate the action of hallucinogenic agents.
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PMID:Differential interactions of indolealkylamines with 5-hydroxytryptamine receptor subtypes. 213 86

Application of serotonin to the isolated, hemisected frog spinal cord resulted in two distinctive changes in motoneuron membrane potential: hyperpolarizations were produced by low concentrations (0.01-1.0 microM) and depolarizations by higher concentrations (3.0-100 microM). The hyperpolarizations appeared to be caused by a direct action of the amine upon motoneurons since exposure of spinal cord tetrodotoxin or magnesium ions in concentrations which blocked interneuronal firing and synaptic transmission, respectively did not reduce these responses. In contrast, depolarizations were significantly reduced by tetrodotoxin or magnesium indicating a large indirect component. The use of agonists and antagonists known to discriminate among different subtypes of serotonin receptors indicated that the hyperpolarizations were produced by activation of 5-HT1A receptors and the depolarizations were generated by activation of 5-HT2 and/or 5-HT1C receptors. Accordingly, the selective 5-HT1A agonists 8-hydroxy-2-(n-dipropylamino)tetralin and ipsapirone directly hyperpolarized motoneurons. The changes in potential produced by low concentrations of serotonin and by these agonists were blocked by the 5-HT1A receptor antagonists spiperone and spiroxatrine. In contrast, application of high concentrations of alpha-methyl-5-hydroxytryptamine, a serotonin analog which activates 5-HT1C and 5-HT2 receptor subtypes, depolarized motoneurons. These depolarizations, and those produced by high concentrations of serotonin, were blocked by the 5-HT1C/5-HT2 antagonists ketanserin, methysergide and mianserin. These observations indicate that serotonin can alter the membrane potential of motoneurons directly and indirectly by activation of both 5-HT1 and 5-HT2 receptor subtypes. Activation of different receptor subtypes depends upon the concentration of the amine.
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PMID:Changes in membrane potential of frog motoneurons induced by activation of serotonin receptor subtypes. 214 Nov 11

In a previous study prolonged low-frequency muscle stimulation in the hind leg of the spontaneously hypertensive rat (SHR) was shown to induce a reduction in blood pressure (about 15 mmHg) that lasted for many hours. We showed in that study that endorphin and serotonin systems were involved. In the present study drugs with selective affinity for the serotonin (5-HT) receptors were used to analyse further the involvement of different serotonin systems. In one group of SHR, a prestimulatory dose of metitepine maleate (a 5-HT1 and 5-HT2 receptor antagonist) completely abolished the post-stimulatory depressor response. The long-lasting depressor response was still present, although less pronounced, after a bolus dose of the 5-HT2 blocking agent ritanserin (R 55667) at the start of stimulation. The 5-HT3 receptor antagonist ICS 205-930 did not influence the response at all, nor did the selective 5-HT1a receptor agonist 8-OH-DPAT enhance the depressor response. These results indicate that the reduction in blood pressure after muscle stimulation is mainly mediated by the 5-HT1 receptor.
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PMID:Role of different serotonergic receptors in the long-lasting blood pressure depression following muscle stimulation in the spontaneously hypertensive rat. 214 73

During secondary aggregation, platelets release 5-hydroxytryptamine (5-HT) from their dense granule stores concurrent with arachidonic acid (AA) metabolism. To examine the hypothesis that released 5-HT has a modulatory effect on the metabolism of AA by platelets, we incubated nonaggregating washed human platelets with 5-HT in the presence of [3H]AA. Stimulation with 10(-4) M 5-HT, followed by incubation with 3 microM AA and 1 microCi [3H]AA for 5 min, resulted in a decrease in the formation of thromboxane B2 (TxB2) and 12-hydroxyheptadecatrienoic acid (HHT, P less than 0.05). The same treatment conditions and stimulation with 10(-7) to 10(-4) M 5-HT resulted in an elevation of 12-hydroxyeicosatetraenoic acid (12-HETE) formation (P less than 0.05). Treatment with the monoamine uptake inhibitor imipramine (20 microM) further increased the stimulation of 12-HETE formation observed in the presence of 10(-4) M 5-HT, suggesting that 5-HT may act at the platelet surface. A 5-HT1A receptor agonist, 8-hydroxy-dipropylaminotetralin (DPAT, 10(-6) to 10(-4) M) stimulated the formation of platelet cyclooxygenase (CO) products, whereas (+/-)1-(2,5-dimethoxy-4-iodo phenyl)-amino propane hydrochloride (DOI, 10(-6) to 10(-4) M), a 5-HT2 receptor agonist, had no significant effect on CO product formation. In addition, the 5-HT2 receptor antagonist ketanserin (10(-7) M) did not block the changes in CO or lipoxygenase metabolism induced by 5-HT. Since both DOI and DPAT stimulated 12-HETE formation whereas ketanserin was unable to reverse the 5-HT-enhanced 12-HETE formation, it seems unlikely that the stimulation of a 5-HT2 receptor is responsible for this action of 5-HT on platelets. We conclude that 5-HT depresses CO product formation while increasing 12-HETE formation through interaction with a platelet serotonergic binding site other than the 5-HT2 receptor.
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PMID:5-Hydroxytryptamine and the metabolism of arachidonic acid by the lipoxygenase and cyclooxygenase of washed human platelets. 214 82

1. The possibility of 5-HT2 receptor modulation of central 5-HT1A receptor function has been examined using the 5-hydroxytryptamine (5-HT) behavioural syndrome induced by 5-HT1A receptor active drugs in rats. 2. The 5-HT2/5-HTIC antagonist ritanserin (0.1-2 mg kg-1) increased the 5-HT behavioural syndrome induced by submaximally effective doses of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) and gepirone. 3. Pretreatment with the 5-HT2/5-HT1C antagonist ICI 170,809 (0.25-5 mg kg-1) also enhanced the behavioural syndrome induced by 8-OH-DPAT or 5-MeODMT. 4. The 5-HT2/alpha 1-adrenoceptor antagonist ketanserin in a low dose (0.25 mg kg-1) significantly increased the 5-HT behavioural syndrome induced by 8-OH-DPAT or 5-MeODMT, while in a higher dose (2.5 mg kg-1) this drug decreased the response. Experiments with prazosin indicate that the higher dose of ketanserin might reduce the 5-HT behavioural syndrome through blockade of alpha 1-adrenoceptors. 5. Ritanserin and ICI 170,809 had no effect on apomorphine-induced stereotypy or hyperactivity, indicating that these drugs do not produce non-specific behavioural activation. 6. Ritanserin and ICI 170,809 inhibited quipazine-induced wet dog shakes at doses similar to those enhancing the 5-HT behavioural syndrome. 7. We suggest that ritanserin, ICI 170,809 and ketanserin enhance 5-HT1A agonist-induced behaviour through blockade of an inhibitory 5-HT2 receptor regulating or coupled to 5-HT1A receptor-mediated function.
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PMID:Behavioural evidence for a functional interaction between central 5-HT2 and 5-HT1A receptors. 214 51

To investigate the possible functional relationship between 5-HT1 and 5-HT2 receptors, we studied the effects of a nonselective 5-HT agonist (5-MeO DMT), a 5-HT1A-selective (8-OH-DPAT) and a 5-HT1B/5-HT1C-selective (TFMPP) agonist on the head-twitch behavior induced by the putative 5-HT2-selective receptor agonist (+/-)-DOI. In the mouse (+/-)-DOI produced the head-twitch response in a dose-dependent manner and (-)-DOI was twice as potent as the (+) isomer. Selective 5-HT2 antagonists, ketanserin and spiperone, dose-dependently inhibited the (+/-)-DOI-induced head-twitch response. The nonselective and the 5-HT1A-selective agonists also dose-dependently reduced the behavior, whereas 5-HT1B/5-HT1C-selective agonist (TFMPP) failed to affect the (+/-)-DOI-induced response. Taken together with previously published literature data, we propose a 5-HT1A inhibitory action on the 5-HT2 receptor-mediated response when induced by its selective agonist (+/-)-DOI.
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PMID:Do functional relationships exist between 5-HT1A and 5-HT2 receptors? 214 93

1. Current and voltage recordings were made from antidromically identified motoneurones (MNs) in transverse thoracolumbar spinal cord slices of neonatal rats. 2. Applied by superfusion (10-100 microM) or pressure ejection, 5-hydroxytryptamine (5-HT) elicited a slow depolarization (or inward current) in 81% and a hyperpolarization (or outward current) in 9% of responsive MNs; the responses persisted in a low-Ca2+, high-Mg2+ or tetrodotoxin (TTX)-containing solution. 3. 5-HT induced the occurrence in some MNs of excitatory postsynaptic potentials (EPSPs) or inhibitory postsynaptic potentials (IPSPs), which were reversibly eliminated by TTX, low-Ca2+, high-Mg2+ solution or by the 5-HT2 receptor antagonists ketanserin and spiperone. Also, kynurenic acid and strychnine abolished, respectively, the 5-HT-induced EPSPs and IPSPs. 4. The 5-HT depolarization was associated with increased membrane resistance, was reduced by hyperpolarization and nullified near -100 mV. The extrapolated reversal potential was shifted to a positive direction in elevated [K+]o. 5. The depolarizing response was mimicked by the 5-HT2 receptor agonist (+2-)-1(2,5-dimethyoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) and blocked by 5-HT antagonists methysergide and cyproheptadine and by 5-HT2 antagonists ketanserin and spiperone; methiothepin and MDL 72222 were without effect. 6. The 5-HT hyperpolarization was associated with decreased membrane resistance. The 5-HT1A agonist 8-hydroxy-2-(di-N-propylamino) tetralin hydrobromide (8-OH-DPAT) mimicked the hyperpolarizing response. 7. Single or repetitive (10-30 Hz) electrical stimuli elicited in about 30% of MNs, in addition to a fast EPSP, a slow EPSP with electrophysiological characteristics similar to that of 5-HT induced depolarization. Methysergide and spiperone abolished the slow EPSPs evoked in some of these MNs. 8. It is suggested that 5-HT, acting on 5-HT2 and 5-HT1A receptors, depolarizes and hyperpolarizes the MNs by decreasing and increasing K+ conductance. Additionally, 5-HT activates, via 5-HT2 receptors, excitatory and inhibitory interneurones, thereby indirectly affecting the activity of MNs. More importantly, 5-HT released from intraspinal nerves appears to be the mediator of a slow EPSP in a population of MNs.
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PMID:5-Hydroxytryptamine responses in neonate rat motoneurones in vitro. 215 Aug 62


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