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)

Constriction of carotid arteriovenous anastomoses is a common property of several antimigraine drugs. The present study concerns the effects of tertatolol (0.1, 0.3, 1 and 3 mg/kg i.v.), a novel beta-adrenoceptor antagonist with an agonist action on 5-HT1A receptors, on systemic haemodynamics and carotid blood flow distribution in the anaesthetized pig. Two other beta-adrenoceptor antagonists, one (propranolol) with and one (pindolol) without antimigraine actions, were compared (doses: 0.03, 0.1, 0.3 and 1 mg/kg i.v.) with tertatolol in this animal experimental model of migraine. While the beta-adrenoceptor antagonist with partial agonist action, pindolol, increased heart rate and cardiac output, propranolol and tertatolol decreased these variables moderately. Mean arterial blood pressure also decreased with the two highest doses of propranolol and with the highest dose of tertatolol. The calculated total peripheral conductance decreased with the first three doses of tertatolol. Carotid haemodynamic variables were not affected by pindolol, except for some increase in the nutrient fraction after the highest dose. Propranolol and especially tertatolol decreased both total carotid blood flow and arteriovenous anastomotic blood flow without affecting the nutrient fraction. In the case of tertatolol, blood flow decreases were accompanied by similar decreases in vascular conductance, indicating active arteriovenous anastomotic constriction. It is therefore suggested that tertatolol may prove effective in the treatment of migraine.
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PMID:Effects of tertatolol, a beta-adrenoceptor antagonist with agonist affinity at 5-HT1A receptors, in an animal model of migraine: comparison with propranolol and pindolol. 135 48

Idazoxan (10 mg/kg, i.p.) produces an unexpected increase in food intake in freely-feeding rats which has been linked to its high affinity for non-adrenoceptor idazoxan binding sites. In this study, a dose-related antagonism of idazoxan-induced food intake by the beta-adrenoceptor antagonist (-)-propranolol (5-20 mg/kg, i.p.), which also blocks 5-HT1 (5-hydroxytryptamine1) receptors has been demonstrated. (+)-Propranolol (10, 20 mg/kg, i.p.) did not attenuate idazoxan-induced feeding. (-)-Propranolol (10 mg/kg, i.p.) but not the (+)-enantiomer (10 mg/kg, i.p.) also significantly inhibited the food intake, induced by the 5-HT1A agonist 8-OH-DPAT (0.25 mg/kg, i.p.). Idazoxan-induced feeding was not altered by the selective beta-adrenoceptor antagonists betaxolol (beta 1; 5 mg/kg, i.p.) and ICI 118,551 (beta 2; 5 mg/kg, i.p.) but was potentiated by the 5-HT receptor antagonist metergoline (5 mg/kg, i.p.). The anomalous findings with metergoline may reflect its action at different sub-types of 5-HT receptor. The water intake induced by idazoxan and the peripherally-active alpha 2-adrenoceptor antagonist L-659,066 was also blocked in a stereoselective manner by propranolol (10 mg/kg) but not significantly by either metergoline (5 mg/kg, i.p.), the beta 1-adrenoceptor antagonist betaxolol (5 mg/kg, i.p.) nor by the beta 2-adrenoceptor antagonist ICI 118,551 (5 mg/kg, i.p.). These results suggest that the food intake induced by idazoxan (and perhaps mediated by non-adrenoceptor idazoxan binding sites) may involve the 5-HT system, although further studies, using antagonists acting selectively at the different sub-types of 5-HT receptor, are required to confirm this.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Are 5-HT receptors or beta-adrenoceptors involved in idazoxan-induced food and water intake? 136 65

In the present study, we examined the clonic seizure immediately preceding head-weaving behaviour elicited by 8-OH-DPAT (40 mg/kg, ip) administration in mice. 8-OH-DPAT, known to be a central 5-HT1A receptor agonist, can induce a clonic seizure. Propranolol (1, 5, 10 mg/kg, ip) and methysergide (10, 20 mg/kg, ip) reduced 8-OH-DPAT (40 mg/kg, ip)-induced head-weaving behaviour and clonic seizure, while ketanserin (125, 250, 500 micrograms/kg, ip) was without effect. Trimethadione (500 mg/kg, sc) and phenobarbital (70 mg/kg, sc) completely inhibited clonic seizure and partially inhibited the head-weaving behaviour. Morphine (50 mg/kg, sc) completely inhibited both 8-OH-DPAT-induced head-weaving behaviour and clonic seizure. These effects of morphine are naloxone (20 mg/kg, sc)-reversible. These results suggest that the clonic seizure immediately preceding head-weaving behaviour elicited by 8-OH-DPAT is mediated mainly by serotonergic receptor 1A and also by additional factors.
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PMID:[8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)-induced clonic seizure in mice]. 183 45

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 mechanisms by which imipramine and dihydroergosine stimulate the 5-HT syndrome in rats and inhibit the head-twitch response in rats and mice were studied. Imipramine- and dihydroergosine-induced stimulation of the 5-HT syndrome was inhibited stereoselectively by propranolol, a high affinity ligand for 5-HT1 receptor sites, but not by ritanserin, a specific 5-HT2 receptor antagonist. (-)-Propranolol potentiated the inhibitory effect of imipramine, but not of dihydroergosine on the head-twitch response, while ritanserin was without effect. Neither imipramine nor dihydroergosine were able to stimulate the 5-HT syndrome in the animals pretreated with p-chlorophenylalanine. As expected, 8-OH-DPAT, a selective 5-HT1A receptor agonist, stimulated, and 5-HT1B agonists CGS 12066B and 1-(trifluoromethylphenyl)piperazine (TFMPP) failed to stimulate the 5-HT syndrome induced in rats by pargyline and 5-HTP administration. A higher dose of ritanserin inhibited the syndrome. While 8-OH-DPAT alone produced all behavioral components of the 5-HT syndrome, dihydroergosine or imipramine alone even at very high doses never produced tremor or a more intensive forepaw padding as seen when these drugs were given in combination with pargyline and 5-HTP. A single administration of (-)-propranolol also inhibited the head-twitch response. This effect lasted in mice longer than after ritanserin administration. In in vitro experiments dihydroergosine expressed approximately twenty-fold higher affinity for 3H-ketanserin binding sites than imipramine. The results suggest that imipramine and dihydroergosine possess two components--one stimulating the 5-HT syndrome in rats by a presynaptic, presumably 5-HT1A-mediated mechanism, and the other inhibiting 5-HT2 binding sites.
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PMID:Do imipramine and dihydroergosine possess two components--one stimulating 5-HT1 and the other inhibiting 5-HT2 receptors? 211 65

This investigation evaluated the antagonist properties of (-)propranolol, (+)propranolol, metergoline and BMY 7378 on the known effect of 8-OH-DPAT (DPAT) to decrease motion sickness in cats. (-)Propranolol produced a greater decrease in the antiemetic effect of DPAT than did (+)propranolol. Although metergoline produced a decrease in the antiemetic effect of DPAT, the decrease could not be clearly attributed to interactions with 5-HT1A receptors because metergoline alone slightly enhanced motion sickness. Depletion of 5-HT with PCPA produced a weaker, nonsignificant enhancement of motion sickness, while mesulergine had no effect. As neither nonspecific 5-HT receptor blockade with metergoline nor depletion of 5-HT mimicked the antiemetic effect of DPAT, it was concluded that DPAT acts on postsynaptic 5-HT1A receptors to prevent emesis. BMY 7378 alone decreased the incidence of motion sickness. A dose just below this agonist range did not decrease the effects of DPAT.
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PMID:Effects of serotonin antagonists on motion sickness and its suppression by 8-OH-DPAT in cats. 215 Apr 42

5-Hydroxytryptamine (serotonin, 5-HT) stimulates basal adenylyl cyclase activity in membranes from guinea pig or rat hippocampi, but 5-HT inhibits forskolin-stimulated adenylyl cyclase activity in these same membranes. The opposing effects of 5-HT on adenylyl cyclase activity indicate that distinct 5-HT receptors, positively and negatively coupled to adenylyl cyclase, are present in these membranes. Stimulation of adenylyl cyclase activity is mediated by two distinct 5-HT receptors. The receptor with lower affinity for 5-HT, designated as RL, is apparently homologous with a 5-HT receptor present in rat collicular membranes, but it is not homologous with the stimulatory receptor characterized in neuroblastoma hybrid cell (NCB-20) membranes. The receptor with higher affinity for 5-HT is homologous with the 5-HT1A binding site. The magnitude of stimulation by 5-HT1A receptors is variable with respect to stimulation by RL and is sometimes completely absent. Inhibition of forskolin-stimulated adenylyl cyclase activity, in membranes from either rat or guinea pig hippocampus or rat cortex, is a functional correlate of the 5-HT1A binding site. This inhibitory response was used to determine the pharmacological characteristics of drugs that reportedly have high affinity for 5-HT1A binding sites, such as 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine (PAPP) and (-)pindolol. PAPP inhibited adenylyl cyclase activity in guinea pig hippocampal membranes with an EC50 value of 27 +/- 3 nM. (-)Pindolol was a partial agonist in inhibiting adenylyl cyclase activity in guinea pig and rat hippocampal membranes. Because of the low intrinsic activity of (-)pindolol, it was tested as an antagonist of the inhibition produced by 5-HT1A receptor agonists in rat hippocampal membranes. The Kb of (-)pindolol was 40 nM as measured by a Schild plot. (-)Propranolol was a simple competitive antagonist at the rat hippocampal receptor with a Kb value of 550 nM. In summary, guinea pig and rat hippocampal membranes possess two distinct populations of 5-HT receptors, a 5-HT receptor that mediates inhibition of adenylyl cyclase activity and is pharmacologically homologous with the 5-HT1A binding site, and a stimulatory receptor that appears to be homologous with the 5-HT receptor first characterized in infant rat collicular membranes.
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PMID:Stimulation and inhibition of adenylyl cyclase by distinct 5-hydroxytryptamine receptors. 222 10

Radioligand binding techniques have demonstrated the existence of 5-hydroxytryptamine (5-HT) binding subtypes: 5-HT2, 5-HT1A and 5-HT1B. These techniques have also indicated that certain drugs appear to show sub-type specificity: 8-hydroxy-2-(di-n-propylamino)tetralin(8-OH-DPAT), a 5-HT1A agonist; 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1-H indole (RU 24969), a 5-HT1B agonist; and ritanserin, a 5-HT2 antagonist. (-)-Propranolol is a 5-HT1 antagonist of uncertain sub-type specificity. An examination has been made in mice and rats of the behavioural and biochemical effects of these drugs to determine whether the binding sites have physiological functions and further characterise the behavioural models. Administration of carbidopa (25 mg kg-1) plus 5-hydroxytryptophan (100 mg kg-1) produced head-twitch behaviour in mice which was antagonized by ritanserin (ED50 = 65 micrograms kg-1) but not (-)-propranolol (20 mg kg-1). 8-OH-DPAT (1-10 mg kg-1 s.c.) and RU 24949 (5 mg kg-1 i.p.) did not produce head-twitch behaviour. 8-OH-DPAT decreased 5-HTP- but not 5-methoxy-N-N-dimethyltryptamine (5 mg kg-1)-induced head-twitch by a (-)-propranolol-insensitive mechanism. Locomotor activity produced in mice by RU 24969 (3 mg kg-1) was antagonized by (-)-propranolol (20 mg kg-1) but not the (+)-isomer. (-)-Propranolol did not antagonize the behaviour induced in rats. In mice, both 8-OH-DPAT and RU 24969 markedly inhibited whole brain 5-HT synthesis and this effect was not antagonized by (-)-propranolol. In rats, 8-OH-DPAT (3 mg kg-1 s.c.) produced all the behavioural changes seen after quipazine (25 mg kg-1). (-)-Propranolol inhibited the behaviour changes produced by both agonists, while ritanserin antagonized the behaviour produced by quipazine but not 8-OH-DPAT. It is concluded, therefore, that the 5-HT1A receptor exists between the 5-HT2 receptor and the behavioural effectors. 8-OH-DPAT (at 20 degrees C ambient temperature) rapidly decreased rat body temperature, an effect antagonized by (-)-propranolol but not ritanserin. Quipazine (at 27 degrees C ambient temperature, but not 20 degrees C) increased body temperature but the effect was not blocked by either antagonist. Ritanserin does not antagonize apomorphine-induced locomotion in either species. 9 We suggest that 5-HT-induced head-twitch behaviour in mice is a useful 5-HT2 receptor model and the temperature change following 8-OH-DPAT injection in rats may be a 5-HT,A model. While (-)- propranolol antagonizes 8-OH-DPAT effects in rat, it does not inhibit 8-OH-DPAT effects in mice, and instead antagonizes RU 24969-induced locomotion. Its status as a 5-HT, antagonist remains illdefined.
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PMID:A behavioural and biochemical study in mice and rats of putative selective agonists and antagonists for 5-HT1 and 5-HT2 receptors. 258 May 82

The effects of serotonin receptor agonists and antagonists on the electrically (3 Hz) evoked 3H overflow were determined on pig brain cortex slices preincubated with 3H-serotonin and superfused with physiological salt solution containing indalpine (an inhibitor of serotonin uptake) plus phentolamine. The potencies of the serotonin receptor agonists and antagonists were compared with their affinities for 5-HT1A, 5-HT1B, 5-HT1C, and 5-HT1D binding sites in pig or rat tissue membranes; in addition, the potencies of the agonists were compared to their potencies in inhibiting adenylate cyclase activity in membranes of calf substantia nigra. In the superfusion experiments on pig brain cortex slices the following rank orders of potencies were obtained: agonists, serotonin greater than 5-methoxytryptamine = 5-carboxamidotryptamine greater than RU 24969 (5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole) greater than SDZ 21009 (4(3-terbutylamino-2-hydroxypropoxy)indol-2-carbonic-acid-isopr opylester) greater than or equal to yohimbine greater than or equal to cyanopindolol greater than 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) greater than or equal to CGS 12066 B (7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]quinoxaline); ipsapirone and urapidil were ineffective; antagonists (antagonism determined against 5-methoxytryptamine as an agonist), metitepine greater than metergoline greater than mianserin. Propranolol, spiperone or mesulergine did not produce a shift of the concentration-response curve for 5-methoxytryptamine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The pharmacological properties of the presynaptic serotonin autoreceptor in the pig brain cortex conform to the 5-HT1D receptor subtype. 279 14

The release of endogenous glutamate (GLU) elicited by depolarization of rat cerebellum synaptosomes was inhibited potently (pEC30 = 9.77) by 5-hydroxytryptamine (5-HT). The 5-HT action was antagonized by methiothepin (pA2 = 10.37); ketanserin, methysergide, cinanserin and spiperone were ineffective. Exogenous 5-HT also inhibited the release of [3H]-5-HT from cerebellar synaptosomes (pEC30 = 8.73). Methiothepin, but not ketanserin, methysergide, cinanserin or spiperone counteracted the inhibition (pA2 = 9.28). The receptors involved (presynaptic 5-HT heteroreceptors and autoreceptors) were activated by the 5-HT1 agonist RU 24969 (5-methoxy-3-[1,2,3,6-tetrahydropyridin-4-yl]-1H-indole) which showed comparable activity at the two receptor systems. (-)-Propranolol, used as a 5-HT1 antagonist, shifted to the right (pA2 = 8.05) the dose-response curve of 5-HT at the autoreceptors, but was ineffective at the receptors regulating GLU release. On the contrary, the 5-HT1A agonist 8-hydroxy-2-di-N-propylamino)tetralin activated the presynaptic heteroreceptors (pEC30 = 7.98), but was ineffective as a 5-HT autoreceptor agonist. The results allow the following major conclusions: 5-HT receptors are located on GLU terminals in rat cerebellum where they may modulate in an inhibitory way the release of GLU; 5-HT autoreceptors possibly involved in a negative feedback regulation of 5-HT release are present on cerebellar 5-HT nerve endings; 5-HT autoreceptors and heteroreceptors can be pharmacologically differentiated and appear to represent subtypes of the 5-HT1 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential pharmacology and function of two 5-HT1 receptors modulating transmitter release in rat cerebellum. 287 Nov 77


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