Document Detail


5-Hydroxytryptamine-induced Cl- transport is mediated by 5-HT3 and 5-HT4 receptors in the rat distal colon.
MedLine Citation:
PMID:  8867100     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the rat distal colon, 5-hydroxytryptamine (5-HT)-induced Cl- secretion is seen as a rise in short circuit current (Isc). We investigated the 5-HT receptor mediating 5-HT-induced Cl- secretion in the rat distal colon. Rat distal colon was prepared either by stripping away the muscularis propria with the neural ganglia, or by leaving it intact. The tissue was mounted in Ussing chambers and short circuited. 5-HT receptor agonist-induced changes (delta) in Isc were recorded in the presence and absence of 5-HT receptor antagonists. In stripped preparations, the rank order of potency of agonists was: 5-HT > 5-methoxytryptamine > alpha-methyl-5-HT >> 2-methyl-5-HT. 5-HT and 5-methoxytryptamine-induced changes in Isc were antagonized by > or = 0.3 microM tropisetron with pA2 values 6.5 and 6.4, respectively. The 5-HT4 antagonist, SC 53606, antagonized the 5-HT-induced response with a pA2 of 7.2. 5-HT1-like (methysergide), 5-HT1P (N-acetyl-5-hydroxytryptophyl 5-hydroxytryptophan amide (5-HTP-DP)), 5-HT2A (ketanserin) and 5-HT3 (ondansetron) receptor antagonists had no significant effect on the 5-HT response in stripped tissue. 3 microM forskolin, or 10 microM 3-isobutyl-1-methyl-xanthine (IBMX), decreased the EC50 and increased the maximum 5-HT response. The 2-methyl-5-HT and 5-HT-induced delta Isc in the unstripped colon preparation were antagonized by the 5-HT3 antagonist, ondansetron (0.3 nM), and 2-methyl-5-HT activity was abolished by pretreatment with tetrodotoxin. In conclusion, 5-HT-induced delta Isc is neurally mediated via a 5-HT3 receptor, and non-neurally mediated via a 5-HT4 receptor in the rat distal colon.
Authors:
M R Budhoo; R P Harris; J M Kellum
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  European journal of pharmacology     Volume:  298     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1996 Mar 
Date Detail:
Created Date:  1996-12-03     Completed Date:  1996-12-03     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  137-44     Citation Subset:  IM    
Affiliation:
Department of Surgery, Medical College of Virginia, Richmond 23298, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Transport
Chlorides / metabolism*
Colon / drug effects*
Dose-Response Relationship, Drug
Indoles / pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Serotonin / drug effects*
Serotonin / pharmacology*
Serotonin Antagonists / pharmacology
Chemical
Reg. No./Substance:
0/Chlorides; 0/Indoles; 0/Receptors, Serotonin; 0/Serotonin Antagonists; 50-67-9/Serotonin; 89565-68-4/tropisetron

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