Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The behavioural effects of the 5-HT1B receptor agonists, RU 24969 and CGS 12066B, have been investigated in C57/B1/6 mice. 2. RU 24969 (1-30 mg kg-1) produced intense and prolonged hyperlocomotion and other behavioural changes. 3. CGS 12066B caused similar effects, but they were much less pronounced, inconsistent and transient irrespective of whether this drug was given i.p. (1-15 mg kg-1) or i.c.v. (0.2-40 micrograms). However, CGS 12066B (7.5 and 15 mg kg-1) caused a dose-related inhibition of RU 24969 (7.5 mg kg-1)-induced hyperlocomotion indicating that the former is a 5-HT1B partial agonist. 4. RU 24969 (7.5 mg kg-1 i.p.)-induced hyperlocomotion was inhibited by the (-)-, but not (+)-isomers of pindolol (4 mg kg-1) and propranolol (20 mg kg-1) but not by metoprolol (10 mg kg-1) or ICI 118,551 (5 mg kg-1), consistent with an involvement of 5-HT1A or 5-HT1B receptors. 5. The response was not altered by the selective 5-HT1A receptor antagonist, WAY 100135 (5 mg kg-1, s.c.), the 5-HT2A/5-HT2C receptor antagonist, ritanserin (0.1 mg kg-1), the selective 5-HT3 receptor antagonist, ondansetron (1 mg kg-1) or the non-selective 5-HT receptor antagonists methysergide (3 mg kg-1) and metergoline (3 mg kg-1). 6. Although spiroxatrine (0.1 mg kg-1) and ketanserin (1 mg kg-1) inhibited RU 24969-induced hyperlocomotion, these effects were probably due to antagonism of dopamine D2 receptors and alpha 1-adrenoceptors respectively. 7. Taken together, these results indicate that RU 24969-induced hyperlocomotion results specifically from activation of central 5-HTIB receptors.8. Lesioning of 5-HT neurones with 5,7-dihydroxytryptamine (75 microg, i.c.v.) or depletion with pchlorophenylalanine(200 mg kg-1, i.p. for 14 days) had no effect on RU 24969-induced hyperlocomotiondemonstrating that the 5-HTIB receptors involved are postsynaptic and that they do not show super sensitivity.9. The involvement of other monoamine neurotransmitter systems in RU 24969-induced hyperlocomotionwas also examined. The response was inhibited by the al-adrenoceptor antagonist, prazosin(1 mg kg-1), the dopamine DI receptor antagonist, SCH 23390 (0.05 mg kg-1) and the dopamine D2 receptor antagonist, BRL 34778 (0.03 mg kg-1), but not by the M2-adrenoceptor antagonist, idazoxan(1 mg kg-1). Lesioning noradrenergic neurones with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine(100 mg kg-1) markedly attenuated this behaviour. These results show that the hyperlocomotion is expressed via noradrenergic and dopaminergic neurones acting on alpha 1-adrenoceptors, DI and D2 receptors.10. RU 24969 decreased brain concentrations of 5-hydroxyindoleacetic acid whilst simultaneously increasing 5-HT, consistent with the reduction of 5-HT neuronal activity by activation of 5-HTlA and 5-HTIB autoreceptors. RU 24969 increased brain 3-methoxy-4-hydroxyphenylglycol, but not noradrenaline, concentrations which supports the involvement of noradrenergic neurones in the expression of hyperlocomotion. RU 24969 did not alter dopamine, dihydroxyphenylacetic acid or homovanillic acid concentrations in the nucleus accumbens suggesting that the dopaminergic neurones terminating there are not directly involved.
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PMID:Evidence that RU 24969-induced locomotor activity in C57/B1/6 mice is specifically mediated by the 5-HT1B receptor. 830 9

The effect of different serotonin (5-HT) receptor agonists on the release of prolactin (PRL) was investigated in conscious male rats. The 5-HT1 receptor agonists 5-carboxamidotryptamine and RU 24969 stimulated the PRL secretion dose dependently. RU 24969 possessed almost the same potency and efficacy (maximal effect) as 5-HT, while 5-carboxamidotryptamine was more potent and had a higher efficacy. The 5-HT1 + 2 receptor agonist MK 212 stimulated the PRL secretion only at high doses. The 5-HT2 receptor agonist S(alpha)methyl-5-HT and the 5-HT3 receptor agonist 2-methyl-5-HT had minor or no effect on the PRL secretion. The PRL-releasing effect of submaximal doses of 5-carboxamidotryptamine and RU 24969 was blocked by the 5-HT1 + 2 receptor antagonist methysergide and enhanced by other 5-HT agonists, but was unaffected by the 5-HT2 and 5-HT3 receptor antagonists. MK 212, S(alpha)methyl-5-HT, and--in particular--2-methyl-5-HT potentiated the effect of 5-carboxamidotryptamine. Likewise, 2-methyl-5-HT potentiated the effect of RU 24969, while MK 212 or S(alpha)methyl-5-HT had an additive to slightly potentiating effect. The findings show that 5-HT stimulates PRL secretion via 5-HT1 as well as 5-HT2 receptors and that activation of 5-HT2 and 5-HT3 receptors significantly augment the PRL-stimulating effect of 5-HT1 receptor activation. This indicates that the 5-HT receptor subtypes may interact functionally in the mediation of the PRL-releasing effect of the serotonergic system.
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PMID:Effect of selective serotonin receptor agonists on prolactin secretion in male rats. 832 11

The effects of three serotonin [5-hydroxytryptamine (5-HT)] receptor antagonists on cocaine self-administration behavior were investigated. Specifically, the effects of MDL 72222 (a specific 5-HT3 receptor antagonist), ketanserin (a specific 5HT2 receptor antagonist), and methysergide (an aselective 5-HT1/5-HT2 receptor antagonist) on the breaking points reached by rats on a progressive ratio schedule for cocaine reinforcement were examined. Pretreatments with MDL 72222 (7.5-1,920 micrograms/kg, SC), ketanserin (0.4-6.4 mg/kg, IP), and methysergide (2.5-20 mg/kg, IP) failed to alter breaking points from baseline values. Although tested at twice the highest doses previously reported to have significant behavioral effects, the three 5-HT receptor antagonists were without effect. These data suggest that relatively specific blockade of 5-HT receptor subtypes does not influence the reinforcing effects of cocaine.
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PMID:MDL 72222, ketanserin, and methysergide pretreatments fail to alter breaking points on a progressive ratio schedule reinforced by intravenous cocaine. 843 Jan 19

5-Hydroxytryptamine (5-HT) potentiated contractions of isolated rat bronchi evoked by electrical field stimulation (EFS). The degree of potentiation caused by 5-HT was dependent upon concentration of the amine present in the tissue bath. The effects of antagonists selective for different subtypes of the 5-HT receptor on potentiation of EFS-induced contractions by 5-HT were examined. Propranolol, a nonselective beta-adrenoceptor antagonist which can act as a 5-HT1 receptor antagonist, did not inhibit the effect of 5-HT on EFS-induced contractile responses. Similarly, 5-HT3 receptor antagonism with MDL 72222 or ICS 205-930, did not inhibit the facilitatory effects of 5-HT. However, ketanserin, mianserin and spiperone, 5-HT2 receptor antagonists, abolished the effects of 5-HT on EFS-induced responses. These latter results suggested that the potentiation was dependent upon activation of 5-HT2 receptors thus additional experiments were conducted using the 5-HT2 receptor agonist, alpha-methyl-5-hydroxytryptamine (alpha-Me-5-HT). alpha-Me-5-HT caused a concentration-dependent potentiation of EFS-induced contractile responses comparable to that observed with 5-HT. Concentrations of alpha-Me-5-HT that significantly potentiated EFS-induced contraction were essentially without effect on airway smooth muscle contraction elicited by exogenous acetylcholine. These results are consistent with a role for 5-HT2 receptor activation in mediating the facilitatory effects of 5-HT on cholinergic nerve-mediated responses in airways.
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PMID:5-HT2 receptors augment cholinergic nerve-mediated contraction of rat bronchi. 844 26

Besides the important role of emotional factors in the production of psychological-stress-induced analgesia (PSY-SIA), recent attention to the participation of serotonergic (5-HTnergic) neurons in the fear- and anxiety-evoking mechanism led us to examine the effects of 5-HTnergic ligands on PSY-SIA. Pretreatment of mice with 2.0 to 10 mg/kg of methysergide, a 5-HT receptor antagonist, or 1.0 to 10 mg/kg of buspirone, a 5-HT1A receptor partial agonist, dose-dependently suppressed the production of PSY-SIA. Ritanserin, a 5-HT2 receptor antagonist, 1.0 to 5.0 mg/kg, or Y-25,130, a 5-HT3 receptor antagonist, 0.03 and 0.1 mg/kg, also inhibited PSY-SIA dose-dependently, while (+/-)pindolol, a 5-HT1A/1B receptor antagonist, was ineffective at doses up to 3.0 mg/kg. Furthermore, the suppressive effect of PSY-stress on the development of antinociceptive tolerance to morphine was also antagonized by methysergide, buspirone, ritanserin and Y-25,130, but not by (+/-)pindolol. These results suggest that 5-HT receptor (5-HT1A, 5-HT2 and 5-HT3 but not 5-HT1B)-mediated mechanisms play an important role in the production of PSY-SIA.
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PMID:Involvement of serotonergic receptor subtypes in the production of antinociception by psychological stress in mice. 848 1

The binding properties of a new radioligand, [methyl-3H]-(-)-(R)-5-[(1-methyl-1H-indol-3-yl)carbonyl]-4,5,6,7- tetrahydro-1H-benzimidazole monohydrochloride ([3H]YM060), were studied in membranes of the rat cerebral cortex. [3H]YM060 rapidly associated with its binding sites in membranes and reversibly dissociated. Saturation analysis revealed that the specific binding of [3H]YM060 was saturable and non-specific binding was low. Scatchard analysis yielded a linear plot, suggesting a single population of binding sites with a dissociation constant (Kd) of 8.4 +/- 0.2 pM (n = 3) and the kinetic Kd determined from the association constant (K+1) and the dissociation rate constant (K-1) was similar. The maximum number of binding sites (Bmax) was 37.0 +/- 0.8 fmol/mg protein (n = 3). [3H]YM060 binding was potently and stereospecifically inhibited by serotonin (5-HT)3 receptor agonists and antagonists. Other 5-HT receptor ligands such as 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), methysergide and ketanserin were inactive to inhibit specific binding at 10(-4) M. These results suggest that [3H]YM060 is a highly potent and selective 5-HT3 receptor radioligand and will be useful in the further analysis of 5-HT3 receptors.
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PMID:Characterization of [3H]YM060, a potent and selective 5-HT3 receptor radioligand, in the cerebral cortex of rats. 856 14

The influence of serotonin (5-hydroxytryptamine, 5-HT) on human ureteral smooth muscle was explored in a series of in vitro experiments. 5-HT evoked a dose-dependent contraction of the ureter. The effect of 5-HT was unaltered by blockade of 5HT3 and 5HT4 receptors and muscarinic cholinergic receptors. The 5HT2 receptor antagonist ketanserin (KT; 10(-5)-10(-4) M) and mixed 5HT1/5HT2 receptor antagonist methysergide (MS; 5 x 10(-5) M) inhibited the effect of 5-HT. Since the antagonist dissociation constant at 5HT2 receptors for both KT and MS is found to be approximately 10(-9) M, it is concluded that this contractile effect may have been mediated by some other, as yet uncharacterized 5-HT receptor. We believe that 5-HT is a potential neurotransmitter in the human upper ureteral smooth muscle.
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PMID:Influence of serotonin on the human ureter: an in vitro pharmacological study. 858 66

The carotid sinuses, one of the major sites of baroreceptor innervation, are also a common site of atherosclerotic lesions and platelet aggregation. The goal of the present study was to determine whether platelet activation in carotid sinuses causes reflex-mediated changes in renal sympathetic nerve activity and arterial pressure. Rabbit platelets were isolated, resuspended in Krebs' buffer, and activated by thrombin. Injection of activated platelets (3 x 10(8) platelets/mL) into the vascularly isolated carotid sinuses of anesthetized rabbits essentially eliminated sympathetic nerve activity and acutely decreased mean arterial pressure from 126 +/- 5 to 53 +/- 4 mm Hg (n=16; P < .05). Sympathetic activity and arterial pressure returned to control levels over a period of minutes despite sustained exposure to activated platelets. Injection of U-46619, a thromboxane analogue and vasoconstrictor, into carotid sinuses did not alter sympathetic activity or arterial pressure. However, serotonin (5-hydroxytryptamine [5-HT]), which is known to be released from activated platelets, and the 5-HT3 receptor agonist phenylbiguanide mimicked the effect of platelets. Furthermore, the platelet-induced reflex inhibition of sympathetic activity and hypotension were not altered by the cyclooxygenase inhibitor indomethacin but were attenuated significantly by 5-HT receptor antagonists. Platelet activation inhibited sympathetic activity to 5 +/- 2% of control in the absence of antagonists but to only 35 +/- 11 and 76 +/- 4% of control after selective blockade of 5-HT2 and 5-HT3 receptors with ketanserin and MDL-72222, respectively. The results indicate that (1) platelet activation in carotid sinuses triggers reflex inhibition of sympathetic nerve activity and hypotension; (2) the reflex is not caused by carotid vasoconstriction and is not mediated by prostanoids; and (3) the reflex is mediated by 5-HT acting primarily on 5-HT3 and to a lesser extent on 5-HT2 receptors. We speculate that this reflex may contribute to arterial pressure lability and susceptibility to stroke in patients with carotid atherosclerotic disease.
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PMID:Platelet activation in carotid sinuses triggers reflex sympathoinhibition and hypotension. 861 8

5-Hydroxytryptamine (5-HT) has a variety of biological effects, e.g. it induces and modulates vascular smooth muscle activity. The effects are mainly mediated via a hetergenous group of 5-HT receptor subtypes. In order to elucidate the 5-HT receptor mechanisms in the human splanchnic circulation, in vitro studies were carried out on omental arteries obtained from patients undergoing abdominal surgery. Four 5-HT receptor agonists with different selectivity all induced concentration-dependent contraction (potency and order of potency indicated): 5-HT (non-selective; 6.12 +/- 0.14)=sumatriptan (5-HT1; 6.32 +/- 0.07) > alpha-methyl-5-HT (5-HT2; 5.41 +/- 0.05) > 2-methyl-5-HT (5-HT3; < or =4.46+/-0.05). The 5-HT1/5-HT2 receptor antagonist methiothepin antagonised the contraction induced by 5-HT, sumatriptan, alpha-methyl-5-HT and 2-methyl-5-HT. The 5-HT2 receptor antagonist ketanserin antagonised the contraction induced by 5-HT, alpha-methyl-5-HT and 2-methyl-5-HT. The 5-HT3 receptor antagonist tropisetron did not antagonise the contraction elicited by 2-methyl-5-HT. The results suggest that 5-HT-induced conataction in human omental arteries involves both 5-HT1 and 5-HT2, but maybe not 5-HT3-receptors.
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PMID:Characteristics of contractile 5-HT receptors in isolated human omental arteries: presence of 5-HT1 and 5-HT2 receptors. 868 87

The memory effects of agonists and antagonists of some serotonin (5-HT) receptor subtypes were examined in experiments on rats using an active avoidance method (shuttle-box). The 5-HT receptor antagonists NAN 190 (1 mg/kg i.p.) and pindolol (6 mg/kg i.p.) improved some indices for memory; the 5-HT2 and 5-HT3 receptor antagonists ritanserin (1 mg/kg i.p.) and ondansetron (0.1 mg/kg i.p.) exerted a favourable effect on the mastering of active avoidance performance. The tryptophan hydroxylase inhibitor para-chlorophenylalanine (300 mg/kg i.p.) alone produced no significant changes in the indices for retention of learned behaviour but in combination with the 5-HT-receptor agonists and antagonists influenced some of their effects. The results obtained show different participation of 5-HT1A, 5-HT2 and 5-HT3 receptors in the mechanisms of the memory process; the nature of this involvement is modulated by the brain level of serotonin.
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PMID:Participation of different 5-HT receptors in the memory process in rats and its modulation by the serotonin depletor p-chlorophenylalanine. 871 54


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