Linked Life Data

8840129

Source:http://linkedlifedata.com/resource/pubmed/id/8840129

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1997-1-15
pubmed:abstractText
The pathways and possible transmitters involved in the contractile response to selective 5-HT3 and 5-HT4 receptor stimulation in the guinea-pig proximal colon were studied. In the presence of methysergide, 5-HT induced contractions, yielding a biphasic concentration-response curve that was changed into a monophasic curve in the presence of the 5-HT3 receptor antagonist, granisetron (1 microM) (low-affinity phase blocked), or the 5-HT4 receptor antagonist, SB 204070 ((1-butyl-4-piperidinyl methyl)-8-amino-7-chloro-1,4-benzodioxan-5-carboxylate) (10 nM) (high-affinity phase blocked) combination of the two antagonists abolished the contraction to 5-HT. The effectiveness and selectivity of both antagonists was confirmed by testing them against contractions in response to the 5-HT3 receptor-selective agonist, 2-methyl-5-HT, and the 5-HT4 receptor-selective agonist, 5-methoxytryptamine. Hexamethonium (100 microM) did not affect the 5-HT3 receptor-mediated contractions, whereas tetrodotoxin (0.3 microM) caused only slight inhibition. Both in the absence and presence of tetrodotoxin, atropine (0.3 microM) inhibited the 5-HT3 receptor-mediated contractions. Hence, the contractions to 5-HT are partly mediated by 5-HT3 receptors that are localized on the nerve endings of the motor neurons. Hexamethonium halved the 5-HT4 receptor-mediated contractions, whereas tetrodotoxin abolished them. The 5-HT4 receptor-mediated contractions were inhibited by atropine (0.3 microM). Thus, the 5-HT4 receptors seem to be localized in the soma of the motor neurons; they also occur on interneurons. The remaining contractions induced by 5-HT3 and 5-HT4 receptor stimulation in the presence of atropine were almost completely inhibited by the tachykinin NK1 receptor antagonist, CP 96345 ((2S,3S)-cis-2-(diphenyl methyl)-N-[(2-methoxy phenyl)-methyl]-1-azabicyclo-[2.2.2]-octan-3-amine) (0.1 microM). CP 96345 also abolished or strongly inhibited contractions in response to substance P (10 nM) and to neurokinin A (30 nM), but neither granisetron nor SB 204070 affected them. Hence, stimulation of either 5-HT3 or 5-HT4 receptors induced contractions that are partially mediated by acetylcholine, and partially by a tachykinin NK1 receptor-stimulating neurotransmitter, probably substance P and/or neurokinin A.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
308
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
173-80
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
5-HT3 and 5-HT4 receptors and cholinergic and tachykininergic neurotransmission in the guinea-pig proximal colon.
pubmed:affiliation
Department of Gastrointestinal Pharmacology, Janssen Research Foundation, Beerse, Belgium.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro