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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1-2
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pubmed:dateCreated |
1992-9-29
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pubmed:abstractText |
In the rat, intravenous (i.v.) serotonin (5-HT) is a noxious stimulus which produces distinct vagal afferent-mediated pseudoaffective responses, a passive avoidance behavior, a vagal afferent-mediated inhibition of the nociceptive tail-flick (TF) reflex and a complex triad of cardiovascular responses. In the present study, we have used a variety of 5-HT receptor antagonists to characterize the receptor subtype(s) in the rat that mediate (1) inhibition of the TF reflex and (2) the cardiovascular responses produced by i.v. 5-HT. 5-HT produced a dose-dependent (3-72 micrograms/kg, i.v.) inhibition of the TF reflex (ED50 = 15.3 +/- 0.7 micrograms/kg). Following administration of the 5-HT2 receptor-selective antagonists ketanserin (50-250 micrograms/kg, i.v.) or xylamidine (10-100 micrograms/kg, i.v.), or the 5-HT3 receptor-selective antagonists ICS 205-930 (50-250 micrograms/kg, i.v.) or MDL 72222 (25-250 micrograms/kg, i.v.), there appeared to be a parallel shift of the 5-HT dose-response curve to the right. Following co-administration of xylamidine (50 micrograms/kg, i.v.) with ICS 205-930 (100 micrograms/kg, i.v.), the 5-HT-induced inhibition of the TF reflex was completely abolished at all doses of 5-HT tested (3-288 micrograms/kg, i.v.). In contrast, administration of the centrally acting 5-HT2 receptor-selective antagonist LY 53857 (10-100 micrograms/kg, i.v.) or the non-specific receptor antagonist methysergide (25-500 micrograms/kg, i.v.) resulted in a dose-dependent, but not parallel shift of the 5-HT dose-response curve to the right. The maximal doses of LY 53857 and methysergide tested (250 micrograms/kg and 500 micrograms/kg, respectively) completely abolished the effects of 5-HT (3-288 micrograms/kg, i.v.). Administration of the alpha 1-adrenoceptor antagonist prazosin (25-100 micrograms/kg, i.v.) failed to alter the 5-HT dose-response curve, indicating that the effects of ketanserin were due to blockage of 5-HT2 receptors rather than alpha 1 receptors. Administration of each of the antagonists also produced marked, but selective effects on components of the complex cardiovascular response to i.v. 5-HT. Each of the 5-HT3 receptor selective antagonists (ICS 205-930 or MDL 72222) produced a dose-dependent attenuation of the Bezold-Jarisch reflex-mediated hypotension and bradycardia, and each of the 5-HT2 receptor selective antagonists (xylamidine, ketanserin or LY 53857) produced a dose-dependent attenuation of the pressor response. The non-specific 5-HT receptor antagonist methysergide produced a dose-dependent attenuation of the 5-HT-induced pressor response.(ABSTRACT TRUNCATED AT 400 WORDS)
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Methysergide,
http://linkedlifedata.com/resource/pubmed/chemical/Prazosin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Antagonists
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0006-8993
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
585
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
71-86
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:1511336-Animals,
pubmed-meshheading:1511336-Blood Pressure,
pubmed-meshheading:1511336-Heart Rate,
pubmed-meshheading:1511336-Injections, Intravenous,
pubmed-meshheading:1511336-Male,
pubmed-meshheading:1511336-Methysergide,
pubmed-meshheading:1511336-Neural Inhibition,
pubmed-meshheading:1511336-Neurons, Afferent,
pubmed-meshheading:1511336-Nociceptors,
pubmed-meshheading:1511336-Prazosin,
pubmed-meshheading:1511336-Rats,
pubmed-meshheading:1511336-Rats, Inbred Strains,
pubmed-meshheading:1511336-Receptors, Serotonin,
pubmed-meshheading:1511336-Reflex,
pubmed-meshheading:1511336-Serotonin,
pubmed-meshheading:1511336-Serotonin Antagonists,
pubmed-meshheading:1511336-Vagus Nerve
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pubmed:year |
1992
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pubmed:articleTitle |
Vagal afferent-mediated inhibition of a nociceptive reflex by i.v. serotonin in the rat. II. Role of 5-HT receptor subtypes.
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pubmed:affiliation |
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City 52242.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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