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. 1993 Dec;110(4):1593–1599. doi: 10.1111/j.1476-5381.1993.tb14006.x

The guinea-pig distal colon--a sensitive preparation for the investigation of 5-HT4 receptor-mediated contractions.

K A Wardle 1, G J Sanger 1
PMCID: PMC2175885  PMID: 8306106

Abstract

1. Experiments were designed to characterize pharmacologically the contractile responses to 5-hydroxytryptamine (5-HT) in the guinea-pig isolated distal colon longitudinal muscle-myenteric plexus preparation (LMMP). 2. In the presence of methiothepin (100 nM) and granisetron (1 microM), 5-HT (10 pM-10 nM) produced concentration-dependent contractile responses of the guinea-pig distal colon LMMP, with a pEC50 of 9.2 +/- 0.08. 3. Responses to 5-HT were mimicked by a series of tryptamine analogues, with the following rank order of potency; 5-HT > 5-MeOT >> 5-CT > tryptamine > 2-Me-5-HT. All were found to be full agonists. 4. Responses to 5-HT were also mimicked by a series of substituted benzamide analogues. Their rank order of potency was 5-HT > renzapride > cisapride > (S)-zacopride > (R)-zacopride > metoclopramide. All were full agonists relative to 5-HT. 5. The benzimidazolone derivatives, BIMU 1 and BIMU 8 were approximately equipotent partial agonists (intrinsic activities of 0.8 +/- 0.07 and 0.5 +/- 0.08 respectively) in the guinea-pig distal colon. 6. Tropisetron produced a rightward displacement of the 5-HT concentration-effect curve, yielding an apparent pA2 of 6.4 +/- 0.1. The slope of the Schild plot (1.3 +/- 0.1) was significantly greater than unity. 7. SDZ 205,557 produced a concentration-dependent shift to the right of the 5-HT concentration-response curve, yielding an estimated pA2 of 7.8 +/- 0.1 and a slope which did not significantly deviate from unity.(ABSTRACT TRUNCATED AT 250 WORDS)

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