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)

Acute administration of gepirone, a 5-HT1A agonist, caused a dose dependent (1-10 mg/kg, IP) reduction in the locomotor activity (open and closed arms) of rats tested in the elevated plus-maze. However, rats housed in individual cages and submitted to chronic treatment with gepirone (10 mg/kg PO) showed a marked increase in the percentages of number and time spent in the open arms as compared to controls. These results are compatible with the idea that the antiaversive effect due to long-term treatment with 5-HT1A agonists is the result of a progressive desensitization of the somatodendritic 5-HT autoreceptor with the consequent recovery of firing rate of 5-HT neurons along with an activation of normosensitive postsynaptic 5-HT neurons. Ketanserin caused a biphasic effects on the exploratory behavior of rats in the plus-maze. The lower dose (0.5 mg/kg) decreased the aversion to the open arms and the higher dose (1.0 mg/kg) caused an unspecific decrease in the overall activity of the animals. Ketanserin is supposed to have antagonistic action on 5-HT2 and on alpha-adrenergic receptors. As prazosin (0.5-1.0 mg/kg), an alpha-adrenergic receptor blocker, did not present any significant effect in the present work it is suggested that the effects of the lower dose of ketanserin was due to its high antagonistic action on 5-HT2 receptors.
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PMID:Effects of blockade of 5-HT2 receptors and activation of 5-HT1A receptors on the exploratory activity of rats in the elevated plus-maze. 135 Mar 49

Serotonin (5-HT) responses of pyramidal neurones freshly dissociated from rat ventral hippocampal CA1 region were investigated by using nystatin-perforated whole-cell recording. These dissociated neurones lack most of the dendrites and axons. Application of nanomolar concentrations of 5-HT induced outward current with an increase of membrane conductance at a holding potential (VH) of -40 mV. The current was mimicked by alpha-methyl-5-HT (5-HT2 receptor family agonist), but not by 8-OH-DPAT (5-HT1 receptor family agonist). Ketanserin (5-HT2 receptor family antagonist) and spiperone (5-HT1A and 5-HT2 receptor family antagonist) blocked the current in a concentration dependent manner. These results suggests that 5-HT-induced outward current is mediated by the activation of 5-HT2 receptor family in the cell bodies of hippocampal pyramidal neurones.
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PMID:5-HT response of rat hippocampal pyramidal cell bodies. 142 Nov 22

The aim of the present experiments was to investigate whether 8-OH-DPAT, a selective 5-HT1A agonist, could induce vasoconstriction in vivo and, if so, the type of receptors functionally involved. Dose-response curves to bolus intravenous doses of 8-OH-DPAT were established in anesthetized spinally pithed rats. The peak increase in the mean arterial pressure-log dose (microgram/kg) relationship was fitted to a sigmoidal logistic equation. In the control group, the dose-response curve was steep. The half maximal dose was 743 micrograms/kg. The maximal response was 43 mmHg. Ketanserin, a potent 5-HT2 and alpha 1-adrenoceptor antagonist (0.25 mg/kg), essentially abolished the effect of 8-OH-DPAT (maximal rise = 6 mmHg). Ritanserin (0.25 mg/kg) and LY 53857 (100 micrograms/kg), which have relatively weak affinity for alpha 1-adrenoceptors, also markedly reduced the pressor action of 8-OH-DPAT (maximal rise 17 and 9 mmHg). Prazosin, an alpha 1-adrenoceptor antagonist, slightly reduced the maximal response to 8-OH-DPAT (22% reduction). Adrenalectomy did not affect the pressor response (42 mmHg). This excluded a contribution of an acute release of adrenaline in the blood pressure elevation. (-)Propranolol (5 mg/kg), a beta-blocker with a 5-HT1A antagonistic action, affected the 8-OH-DPAT-induced blood pressure elevation (37% reduction). However, two other beta-blockers with a similar 5-HT1A antagonistic property, (-)pindolol (5 mg/kg) and (+/-)cyanopindolol (10 mg/kg), did not (maximal rise 44 and 39 mmHg). Finally, 8-OH-DPAT dose-dependently increased local vascular resistances, with a regional profile similar to that of 5-HT, with the hindquarter being the most sensitive vascular bed. Ketanserin also prevented the vascular effects of 8-OH-DPAT. Our pharmacological analyses of the vascular action of 8-OH-DPAT in the spinally pithed rat indicated that this drug caused dose-related increases in blood pressure. This effect depended on a rise in peripheral vascular resistance, particularly in the hindquarter and kidney beds. Our data suggest that the 5-HT1A agonistic property of 8-OH-DPAT cannot account for this pressor effect which seems to depend on the activation of the vascular 5-HT2 receptor.
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PMID:Evidence that 5-HT2 receptors mediate the pressor effect of 8-OH-DPAT in the spinally pithed rat. 198 65

The purpose of the present study was to characterize the receptor subtypes that mediate serotonin (5-HT)-induced contraction in isolated rat intramyocardial coronary artery. In coronary artery with and without endothelium, only 5-HT and alpha-methylserotonin maleate (5-HT2 agonist) elicited equipotent concentration-dependent contractions. The EC50 values for 5-HT and alpha-methylserotonin maleate in endothelium-intact arteries were 4.7 x 10(-7) and 4.5 x 10(-7) M, respectively, whereas in endothelium-denuded arteries they were 2.8 x 10(-7) and 1.9 x 10(-7) M, respectively. The other subtype agonists, such as (+/-)-8-hydroxy-dipropylaminotetralin hydrobromide (5-HT1A agonist), 1-(3-chlorophenyl)piperazine dihydrochloride and 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrrolo(1,2-a)quinoxaline (5-HT1B) and 2-methyl-serotonin maleate (5-HT3), only elicited a small percentage of the maximum contraction to 5-HT. In prostaglandin F2 alpha-precontracted coronary arteries with intact endothelium or denuded of endothelium, the addition of 5-HT resulted in a further increase in tension. No relaxation was observed with 5-HT up to 1 x 10(-5) M. The contraction induced by 5-HT in artery both with and without endothelium was inhibited by ketanserin (5-HT2 antagonist) but not by l-propranolol (5-HT1 antagonist) nor by 3-tropanyl-indole-3,5-dichlorobenzoate (5-HT3 antagonist). Ketanserin, the selective 5-HT2 antagonist, effectively antagonized 5-HT-induced contraction by shifting the 5-HT response curve to the right without inhibiting the maximal response in both endothelium-intact and -denuded arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of serotonin receptors in isolated rat intramyocardial coronary artery. 198 55

The interactions between 5-hydroxytryptamine (5-HT), 8-hydroxy-2-(N,N-dipropylamino)-tetralin (8-OH-DPAT), buspirone, 2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl)-1,2-benzisothiazol-3- (2H)one-1, 1-dioxide-hydrochloride (TVX Q 7821) and ketanserin, and putative 5-HT receptors were analyzed using both radioligand techniques and an in vitro hippocampal slice preparation. The potencies of the drugs were determined at 5-HT1A binding sites labelled by [3H]8-OH-DPAT in hippocampal membranes from the rat. The binding site had similar affinity for 5-HT, 8-OH-DPAT, buspirone and TVX Q 7821, whereas ketanserin was essentially inactive. Physiological effects of these drugs were also examined using an in vitro hippocampal slice preparation. With the exception of ketanserin, application of each drug to the bath modulated the amplitude of the field potential recorded in the pyramidal layer of CA1 evoked by stimulation of Schaffer collaterals. Application of micromolar concentrations of 5-HT produced an initial increase in the population spike followed by a return to near baseline levels within 5 min. By contrast, the amplitude of the population spike was reduced in a dose-dependent manner by micromolar concentrations of 8-OH-DPAT, buspirone and TVX Q 7821, beginning 5 min after application of drug. Ketanserin did not affect the amplitude of the population spike and it did not antagonize the effects of 5-HT, buspirone or TVX Q 7821. Neither buspirone nor 8-OH-DPAT altered the initial increase in population spike induced by 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of neuronal activity in the hippocampus by 5-hydroxytryptamine and 5-hydroxytryptamine1A selective drugs. 288 86

The effects of the nonbenzodiazepine anxiolytic agents, buspirone, gepirone and ipsapirone on body temperature and corticosterone secretion were studied in the rat. The administration of buspirone, gepirone and ipsapirone resulted in dose-related decreases in body temperature and increases in the plasma concentration of corticosterone. Spiperone produced a dose-related inhibition of the hypothermic and corticosterone responses to gepirone. Spiperone also inhibited ipsapirone-induced changes in body temperature and hormone secretion. Although spiperone also blocked the buspirone-induced stimulation of corticosterone, it did not attenuate the hypothermic response to buspirone at the dose tested. (-)-Pindolol, a potent 5-HT1A antagonist, prevented gepirone- and ipsapirone-induced hypothermia and corticosterone secretion. (-)-Pindolol also blocked the hypothermic but not the corticosterone response to buspirone. Ketanserin, a 5-HT2 antagonist, did not inhibit the hypothermic or corticosterone responses produced by these novel anxiolytic agents. It is concluded that buspirone, gepirone and ipsapirone produce hypothermia and increase plasma concentrations of corticosterone by activating 5-HT1A receptor mechanisms.
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PMID:5-Hydroxytryptamine1A receptor-mediated effects of buspirone, gepirone and ipsapirone. 290 Nov 12

Intravenous administration of the putative 5-HT1-like receptor agonist RU 24969 (10-1000 micrograms/kg) in anaesthetized rats induced a decrease in heart rate and blood pressure. The bradycardia was reduced, but not suppressed, by tertatolol, bilateral vagotomy or the combination of both treatments. The alpha 1-adrenoceptor blocking agent, AR-C 239, decreased the bradycardia induced by high doses of RU 24969. After treatment with hexamethonium, RU 24969 induced an increase in arterial blood pressure. The hypotensive response induced by RU 24969 was not altered by atropine. The hypotensive and bradycardic effects of RU 24969 were antagonized by methysergide (5-HT1-like receptor antagonist) and in part by spiroxatrine (5-HT1A receptor antagonist). Ketanserin (5-HT2 receptor antagonist) potentiated the effects of low doses of RU 24969. The cardiovascular effects of RU 24969 were antagonized neither by MDL 72222 nor by ICS 205-930 (5-HT3 receptor antagonists). The present results suggest that the cardiovascular effects of RU 24969 seem to be due to the stimulation of 5-HT1-like receptors. The participation of both 5-HT1A and 5-HT1B receptors subtypes has been considered. The results suggest a centrally-mediated inhibition of sympathetic tone and increase in vagal tone in the cardiovascular effects of RU 24969.
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PMID:Cardiovascular properties of a 5-HT1-like receptor agonist, 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU 24969) in normotensive anaesthetized rats. 290 24

The effects of serotonergic agonists and antagonists on the body temperatures of rats were investigated. The administration of the serotonin (5-HT) agonist 6-chloro-2(1-piperazinyl)-pyrazine (MK-212) produced a dose-related increase in body temperature. A maximal increase in body temperature of approx. 1.1 degrees C was observed 30 min after the administration of 3 mg/kg of MK-212. In contrast, administration of the putative 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) resulted in marked, dose-related hypothermic responses. Body temperatures were decreased approx. 3 degrees C 30 min after an injection of 0.3 mg/kg of 8-OH-DPAT. Body temperatures were affected differentially by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). Large doses (3-10 mg/kg) of 5-MeODMT elicited hyperthermic responses, whereas small doses (0.5-1.0 mg/kg) produced hypothermic responses. Treatment of rats with ketanserin (3 mg/kg) completely prevented the hyperthermic effects of 5-MeODMT, and, in fact, converted a hyperthermic response to 5-MeODMT into a marked hypothermic response. Ketanserin (0.1-1.0 mg/kg) selectively antagonized the hyperthermic response to MK-212 but did not alter the hypothermic effect of 8-OH-DPAT. Mianserin (10 mg/kg) and pirenperone (0.03 mg/kg) also selectively antagonized hyperthermia induced by MK-212. In contrast, pindolol (0.03-0.1 mg/kg) and methiothepin (10 mg/kg) selectively antagonized hypothermia induced by 8-OH-DPAT but did not alter hyperthermia induced by MK-212. Spiperone (0.1-3 mg/kg) and pizotifen (10 mg/kg) attenuated the effects of both 8-OH-DPAT and MK-212. Xylamidine, a peripheral 5-HT antagonist, had no significant effect on hyperthermia induced by MK-212 or hypothermia induced by 8-OH-DPAT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thermoregulatory responses to serotonin (5-HT) receptor stimulation in the rat. Evidence for opposing roles of 5-HT2 and 5-HT1A receptors. 295 11

Serotonin enhances acetylcholine-elicited contractions of buccal muscle E1 of Aplysia. To characterize the serotonin receptor, actions of ligands of specific serotonin receptor subtypes were examined. Ketanserin, an antagonist at 5-HT2 receptors, had little effect. Two 5-HT1A ligands, LY165163 and 8-OH-DPAT, mimicked the effect of serotonin, although with slower kinetics. This suggests that the peripheral serotonin receptor in Aplysia more closely resembles 5-HT1 than 5-HT2 receptors.
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PMID:LY165163 and 8-OH-DPAT have agonist effects on a serotonin responsive muscle of Aplysia. 295 1

1. The functional significance of subtypes of 5-hydroxytryptamine (5-HT) receptors was studied in the rat spinal reflex pathway. 2. Ketanserin had no effect on the mono- (MSR) or polysynaptic reflex (PSR) in spinal rats, but decreased the PSR in intact rats. 3. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) decreased the MSR and increased the PSR in spinal rats. 4. Ketanserin antagonized the effects of 5-MeODMT without antagonizing the effects of 8-OH-DPAT. 5. Cinanserin had similar effects to those of ketanserin. 6. These results suggest that both 5-HT1A and 5-HT2 receptors mediate MSR inhibition and PSR augmentation in the spinal reflexes of spinal rats, and that the 5-HT2 receptor has a supraspinal tonic excitatory influence on the PSR in intact rats.
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PMID:Functional significance of subtypes of 5-HT receptors in the rat spinal reflex pathway. 297 87


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