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

The prejunctional and postjunctional 5-HT receptors of the canine saphenous vein were studied. The release of 3H-noradrenaline (3H-NA) from incubated saphenous vein strips was inhibited by 5-hydroxytryptamine (5-HT) in a concentration-dependent way (5-HT concentrations: 0.01, 0.1 and 1.0 mumol.l-1), but not by the selective 5-HT1A agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT; 1 and 10 mumol.l-1). The inhibitory effect of 5-HT was antagonized by metitepine and methysergide, but not by yohimbine, (-)-pindolol or ketanserin. In strips preincubated with 5-HT (1.2 mumol.l-1), the fractional release of 3H-NA was slightly reduced (paired experiments). 5-HT and 8-OH-DPAT caused concentration-dependent contractions of the saphenous smooth muscle. A parallel shift of the concentration-response curve for 8-OH-DPAT to the right was caused by metitepine and yohimbine, but not by ketanserin. The contractions caused by 5-HT were antagonized by metitepine and yohimbine (parallel displacement of the curves to the right), as well as by ketanserin and methysergide (with a depression of the upper part of the curve). Blockade of alpha-adrenoceptors (due to prazosin plus a low concentration of yohimbine) also resulted in a weak antagonistic effect. Ketanserin and metitepine displaced the noradrenaline concentration-response curve to the right. We conclude that the saphenous vein of the dog is endowed with prejunctional receptors of the 5-HT1 type which can not be classified as belonging either to the 1A or 1B subtype; and that at the postjunctional level 5-HT1 (possibly of the 1D subtype) and 5-HT2 receptors are present.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The actions of 5-hydroxytryptamine receptor agonists and antagonists at pre- and postjunctional level on the canine saphenous vein. 297 24

1. The excitability of lumbar spinal motoneurones was studied in halothane-anaesthetized rats by recording with microelectrodes the amplitude of the population spike evoked antidromically by stimulation of the cut ventral roots. 2. Electrical stimulation of the nucleus raphe obscurus for 1 min at 20 Hz increased the population spike amplitude and, as shown by intracellular recording, depolarized motoneurones. This response could be mimicked by microinjection of DL-homocysteic acid into raphe obscurus but the response was not present in animals pretreated with the 5-hydroxytryptamine (5-HT) neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). 3. Microiontophoretically applied 5-HT had very similar effects on the extracellularly recorded population spike to those caused by stimulation of the raphe obscurus. These responses to 5-HT were larger in 5,7-DHT-pretreated animals. 4. The effects of 5-HT were potently mimicked by iontophoretically applied 5-carboxamidotryptamine but 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) was without effect. 5. Antagonists were applied by microiontophoresis and also by intravenous injection. Ketanserin, the selective 5-HT2 antagonist, did not antagonize the effects of 5-HT. Neither did the 5-HT3-receptor antagonist MDL 72222 or the selective 5-HT1 binding ligand cyanopindolol. 6. The non-selective 5-HT1/5-HT2-receptor antagonist methysergide was an effective antagonist of both the effects of 5-HT and the response to raphe obscurus stimulation. Methysergide did not reduce the excitatory effects of noradrenaline. 7. It is concluded that 5-HT application and stimulation of raphe obscurus increase the excitability of motoneurones by an action on a 5-HT1-like receptor which appears to be different from the 5-HT1A-and the 5-HT1B-binding sites characterized by others.
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PMID:Effects of 5-hydroxytryptamine agonists and antagonists on the responses of rat spinal motoneurones to raphe obscurus stimulation. 322 71

In the rat inferior vena cava preincubated with 3H-noradrenaline, the effects of nine serotonin (5-HT) receptor agonists and of eight antagonists (including two beta-adrenoceptor blocking agents) on the electrically evoked 3H overflow were determined. 1. 5-HT, 5-carboxamido-tryptamine, 5-methoxy-3(1,2,3,6-tetrahydropyridine-4-yl)-1H-indole (RU 24969), 5-methoxytryptamine, N,N-dimethyl-5HT, tryptamine and 5-aminotryptamine inhibited the evoked 3H overflow. The potencies of these agonists in inhibiting overflow were significantly correlated with their affinities for 5-HT1B binding sites, but not with their affinities for 5-HT1A, 5-HT1C or 5-HT2 binding sites. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, and ipsapirone, a partial agonist at these receptors, did not inhibit overflow. 2. Cyanopindolol facilitated the evoked 3H overflow, an effect which was abolished by propranolol. The maximum inhibition of overflow obtainable with 5-HT was diminished by cyanopindolol. 3. The concentration-response curve for 5-HT was shifted to the right by metitepine, metergoline, quipazine, 6-chloro-2-(1-piperazinyl)pyrazine (MK 212) and propranolol which, given alone, did not affect 3H overflow. The apparent pA2 values of these antagonists tended to be correlated with their affinities for 5-HT1B (but not 5-HT1A, 5-HT1C or 5-HT2) binding sites. Ketanserin, a 5-HT2 receptor antagonist, and spiperone, which blocks 5-HT2 and 5-HT1A but not 5-HT1B or 5-HT1C receptors, failed to antagonize the effect of 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of noradrenaline release via presynaptic 5-HT1B receptors of the rat vena cava. 368 95

1. The effect of 5-hydroxytryptamine (5-HT) was studied on excitatory neurally mediated non-adrenergic non-cholinergic (NANC) contractions evoked by electrical field stimulation (EFS) in guinea-pig isolated bronchi. 2. 5-HT (0.1-100 microM) produced a concentration-dependent inhibition of the excitatory NANC response with 50.9 +/- 5.0% (n = 5, P < 0.01) inhibition at 100 microM. This inhibition was not significantly affected by the 5-HT2 antagonist, ketanserin (1 microM) when inhibitions (+/- ketanserin) at each concentration of 5-HT were compared by unpaired t tests; however, this concentration appeared to produce a leftward shift (approximately 10 fold) of the 5-HT concentration-inhibition curve. Ketanserin (1 microM) was effective in blocking bronchoconstriction evoked by activation of 5-HT2A receptors on airway smooth muscle. In the presence of ketanserin (1 microM) 5-HT (100 microM) evoked an inhibition of 57.4 +/- 5.9% (n = 5, P < 0.01) with an EC50 of 0.57 microM. 3. Inhibition evoked by 5-HT (0.1-100 microM) was unaffected by the alpha-adrenoceptor antagonist phentolamine (1 microM), the beta 2-adrenoceptor antagonist, ICI 118551 (0.1 microM), the 5-HT1A/B antagonist, cyanopindolol (1 microM) or the 5-HT3/4 antagonist, ICS 205-930 (1 microM). 4. Methiothepin (0.1 microM) produced an insurmountable inhibition of the effect of 5-HT (0.1-100 microM), reducing the maximum inhibition produced by 5-HT (100 microM) to 30.2 +/- 5.0% (n = 5, P < 0.001) and suggesting a non-competitive antagonism. Methiothepin inhibited the effect of 5-HT (10 microM) in a concentration-dependent manner with an IC50 of 81 nM. 5. Selective 5-HT receptor agonists were also tested on excitatory NANC responses. 5-Carboxamidotryptamine (5-CT, 0.1-100 MicroM) was the most potent, producing a concentration-dependent inhibition with an EC50 of 0.13 MicroM. Calculation of approximate IC25 values (concentration of the agonist required to give a 25% inhibition of the excitatory NANC response) gave a rank order of potency 5-CT > 5-HT> > 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) >alpha-methyl-5-hydroxytryptamine (alpha-Me-5HT). Sumatriptan, 5-methoxytryptamine (5-MeOT) and 2-methyl-5-hydroxytryptamine (2-Me-5HT) were essentially inactive with IC25> 100 MicroM.6. 5-HT (10 microM) did not significantly affect contractile responses to exogenously applied substance P(1 nM-10 Microm).7. The effect of 5-HT was unchanged after incubation with the nitric oxide (NO) synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME, 100 Microm). However, pretreatment with charybdotoxin (ChTX,0.1-30 nM), a blocker of the large conductance Ca2+-activated K+channel (K+ca), produced a concentration-dependent inhibition of the effect of 5-HT (10 MicroM).8. 5-HT evokes a concentration-dependent inhibition of e-NANC bronchoconstriction in guinea-pig isolated bronchi but does not affect cumulative concentration-dependent contractile responses to substance P, suggesting that inhibition is via a prejunctional receptor. Effects of selective antagonists and agonists suggest that an atypical 5-HT receptor mediates this inhibition. The inhibitory effect of 5-HT does not involve the production of NO, but may involve the opening a ChTX-sensitive K+ca channel.These data suggest that an atypical 5-HT receptor inhibits the release of neuropeptides from sensory C fibres and may act as other inhibitory neuromodulators via the opening of a common K'channel.
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PMID:Inhibition of excitatory non-adrenergic non-cholinergic bronchoconstriction in guinea-pig airways in vitro by activation of an atypical 5-HT receptor. 751 94

In vitro autoradiography was performed on sections of cat brain stem and spinal cord using [3H]sumatriptan. Localization studies using 20-25 nM [3H]sumatriptan showed specific binding to cells in the trigeminal nucleus caudalis and nucleus tractus solitarius of the brain stem and the dorsal horn of the spinal cord. This binding was unaffected by 8-hydroxy-dipropylaminotetralin (20 nM), but was abolished by 5-carboxamidotryptamine (200 nM). Ketanserin displaced total specific binding in the brain stem with a pIC50 of 6.2 but no apparent regional specificity. These results indicate that [3H]sumatriptan labels predominantly 5-HT1D alpha and/or 5-HT1D beta (but not 5-HT1A or 5-HT1F) receptor subtypes in cat brain stem and spinal cord.
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PMID:Autoradiographic mapping of [3H]sumatriptan binding in cat brain stem and spinal cord. 758 83

The effect of serotonin (5-HT) and thyrotropin-releasing hormone (TRH) analogue, p-Glu-His-[3,3'-dimethyl]-Pro-NH2 (RX-77368), injected into the dorsal vagal complex (DVC) on gastric acid secretion was assessed in urethan-anesthetized rats with gastric cannula. 5-HT (0.1, 0.2, 1, or 10 nmol into the DVC) enhanced the acid response to RX-77368 (25 pmol, DVC) by 54, 100, 147, and 144%, respectively, whereas 5-HT given alone had no effect. The 5-HT2 receptor agonists (1 nmol, DVC), ( +/- )-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride, 1-(alpha, alpha, alpha-trifluoro-m-tolyl)-piperazine hydrochloride, and alpha-methyl-5-HT increased the gastric acid response to coinjection of RX-77368 (25 pmol) by 153, 108, and 96%, respectively, whereas 8-hydroxy-2-(di-n-propylamino)tetralin (5-HT1A), 7-trifluoromethyl-4(4-methyl-1-piperazinyl)- pyrrolo[1,2-a]quinoxaline (5-HT1A/1B), and 3-(2-aminoethyl)-2-methyl-1-H-indol-5-ol hydrochloride hydrate (2-methyl-5-HT3) did not. The 5-HT2 receptor antagonist, 3-[2-(4-fluorobenzoyl)-1-piperdinyl]ethyl]-2,4(1H,3H)-quinazoli nedone tartrate (ketanserin; 20 nmol), injected intracisternally abolished the potentiating action of 5-HT injected into the DVC with RX-77368, whereas the 5-HT antagonists 8-[4-(4-fluorophenyl)-4-oxobutyl]-1-phenyl-1,3,8-triazaspiro[4,5]- decan-4-one (spiperone; 5-HT2/1A) and 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1- yl)methyl]-4H-carbazol-4-one hydrochloride dihydrate (ondansetron; 5-HT3) did not. Ketanserin (1 nmol/site bilaterally into the DVC) decreased the acid response to kainic acid injected into the raphe pallidus by 62%. These data suggest that 5-HT acting at 5-HT2 receptors in the DVC potentiates the gastric acid response to exogenous and endogenous TRH.
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PMID:Serotonin enhances gastric acid response to TRH analogue in dorsal vagal complex through 5-HT2 receptors in rats. 763 81

The aim of this study was to characterize, in conscious rats, the spinal cord 5-hydroxytryptamine (5-HT) receptors involved in mean arterial pressure (MAP) and heart rate (HR) regulation as well as to examine the influence of bulbospinal 5-HT fibers on cardiovascular responses to intrathecal (i.t.) substance P (SP). The i.t. injection of 5-HT or 5-carboxamidotryptamine (5-CT) (5-HT1A,1B,1D agonist) reduced MAP and increased HR in a dose-dependent manner. In contrast, the agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 5-HT1A agonist) and alpha-CH3-5-HT (5-HT1C and 5-HT2) only caused a decrease in HR, while the agonist 2-CH3-5-HT (5-HT3) was devoid of cardiovascular effects. The vasodepressor response to 5-CT was antagonized by methiothepin but not affected by mesulergine, ketanserin, propranolol, or yohimbine. However, all five antagonists reduced the HR increase to 5-CT. Ketanserin, propranolol, mesulergine, yohimbine, and methylsergide were without effect on resting MAP, while methiothepin reduced MAP. Methiothepin, ketanserin, and methylsergide increased resting HR, yet the other antagonists had no effect on this parameter. Rats treated with p-chlorophenylalanine or 5,7-dihydroxytryptamine, but not with 6-hydroxydopamine, exhibited higher resting HR than that of control rats. Although the resting MAP was unaffected, the pressor response to i.t. SP was significantly enhanced by either 5-HT toxin. The results suggest that the receptor mediating the depressor response to 5-HT and 5-CT conforms with the broad pharmacological profile of a 5-HT1-like receptor and is unlikely to be of the 5-HT2 or 5-HT3 subtype. Since the HR response evoked by 5-CT was blocked by antagonists that exhibit affinities for various 5-HT receptor subtypes, it is suggested that a nonspecific blockade or, alternatively, that more than one receptor contributes to this cardiac effect. In addition, the results raise the possibility that a spinal 5-HT input, likely mediated by 5-HT2 receptors, tonically inhibits HR. Hence, an antagonistic interaction between 5-HT and SP is proposed to play a role in the control of arterial blood pressure in the spinal cord.
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PMID:Spinal cord serotonin receptors in cardiovascular regulation and potentiation of the pressor response to intrathecal substance P after serotonin depletion. 769 81

1. Serotonin has a facilitary role in the role of corticosterone secretion. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A agonist, dose dependently (0.25- 1.0 mg/kg i.p.) increased rat plasma corticosterone concentration. 2. 3 days parachlorophenylalanine (PCPA) (150 mg/kg) administration did not effect the 8-OH-DPAT-induced corticosterone secretion. 3. Corticosterone responses to 8-OH-DPAT (0.5 mg/kg) were significantly attenuated by pretreatment with propranolol (5 mg/kg). Ketanserin (2 mg/kg), haloperidol (0.2 mg/kg), prazosin (0.1 mg/kg), and ICS-205930 (30 mu/kg) failed to antagonize the corticosterone response to 8-OH-DPAT. 4. 8-OH-DPAT-induced corticosterone were investigated in male rats after treatment with mianserin (2, 10 mg/kg), imipramine (5 mg/kg), desipramine (5 mg/kg), doxepine (5 mg/kg) for 1 day or 3 weeks. Chronic mianserin (10 mg/kg) and doxepine (5 mg/kg) did significantly increase 8-OH-DPAT-induced corticosterone response. Acute antidepressant, chronic imipramine, desipramine and mianserin (2 mg/kg) treatment did not change it. 5. These findings demonstrate that chronic treatment of some antidepressants potentiates 8-OH-DPAT-induced increase in plasma corticosterone, by actions at 5-HT-1A receptors located postsynaptically on 5-HT neurones.
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PMID:Effects of 8-OH-DPAT on corticosterone after acute and chronic administration of antidepressants. 770 35

Blastogenic transformation of murine spleen cells elicited with concanavalin A was suppressed by serotonin 10(-12) to 10(-6) M, and marginally stimulated by its antagonists ketanserin and propranolol in low concentrations (10(-15) to 10(-11) M). Ketanserin (5-HT2 receptor ligand) and propranolol (5-HT1A and beta-adrenergic ligand) did not block the suppressive effect of serotonin if used along with it in equimolar concentrations (10(-9) M). Ergot-alkaloid dihydroergosine suppressed, whereas dihydroergotoxin stimulated the blastogenic transformation. Opposite effects of the agents were obtained in experiments with mouse myeloma X63/Ag 8.653 and hybridoma SHV 125 cell lines, which unlike normal lymphoid cells, are homologous cell populations and proliferate spontaneously. The data indicate that serotonin and its antagonists interfere directly with mitosis and/or autocrine stimulation of target cells.
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PMID:Serotonin and serotoninergic agents affect proliferation of normal and transformed lymphoid cells. 775 68

The present study was designed to investigate the effects of combined stimulation of 5-HT1A or 5-HT2 receptors and blockade of muscarinic acetylcholine receptors on passive avoidance behavior. Administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2 receptor agonist, impaired passive avoidance acquisition (pre-training injections) and consolidation (post-training injections) performance. Ketanserin, a 5-HT2 receptor antagonist, blocked the performance-impairing effect of DOI on passive avoidance consolidation. Interestingly, 5-HT receptor agonists may affect passive avoidance consolidation only during the immediate post-training period, as passive avoidance testing performance was not modulated by 8-OH-DPAT or DOI injected 30 min after the training trial. Furthermore, passive avoidance retention (pre-testing injections) performance was impaired only by the highest dose of 8-OH-DPAT, and DOI had no effect on passive avoidance retention. Next, the effects of combined 5-HT and acetylcholine receptor manipulations on passive avoidance behavior were studied. The effects on passive avoidance behavior of a combination of subthreshold doses of scopolamine, a muscarinic acetylcholine receptor antagonist, and 8-OH-DPAT were compared to those of a single high dose of scopolamine. A combination of small doses of scopolamine and 8-OH-DPAT impaired acquisition and consolidation of passive avoidance performance, but a single high dose of scopolamine impaired only acquisition performance. The small dose of 8-OH-DPAT also aggravated medial septal lesion-induced passive avoidance acquisition and consolidation failure. The combination of small doses of scopolamine and DOI had no effect on passive avoidance behavior. Peripherally acting scopolamine methylbromide alone or in combination with 8-OH-DPAT had no effect on passive avoidance performance. Motor activity in a swimming pool was altered by single and combined drug treatments; high doses of 8-OH-DPAT and scopolamine, and the combination of small doses of 8-OH-DPAT + scopolamine increased speed of swimming. Medial septum-lesioning also increased speed of swimming but the speed was not increased further by 8-OH-DPAT. The present data suggest that behavioral defect caused by hypostimulation of muscarinic acetylcholine receptors is aggravated by concurrent 5-HT1A receptor stimulation.
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PMID:5-HT1A and muscarinic acetylcholine receptors jointly regulate passive avoidance behavior. 781 81


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