Characterization of 5-HT receptors mediating contraction and relaxation of the longitudinal muscle of guinea-pig distal colon in vitro.

A range of agonists and antagonists were used to characterize the receptors through which 5-hydroxytryptamine (5-HT) contracts and relaxes the longitudinal muscle of segments of guinea-pig distal colon, in vitro. 5-HT contracted the longitudinal muscle over the concentration range 10(-9) to 10(-4) mol/l. The 5-HT3 receptor agonist, 2-methyl-5-HT, produced concentration dependent contractions over the range 10(-6) to 10(-4) mol/l. 5-methoxytryptamine, an agonist at 5-HT4 receptors, caused contractions over a concentration range of 10(-8) to 10(-4) mol/l. The 5-HT4 antagonist, SDZ 205-557 (5 x 10(-7) mol/l) substantially suppressed the responses to low concentrations of 5-HT and to 5-methoxytryptamine, but had no effect on the responses to higher concentrations of 5-HT. In contrast, the 5-HT3 antagonist, granisetron (10(-6) mol/l), blocked the effect of 2-methyl-5-HT and substantially depressed responses to high concentrations of 5-HT, but had no effect on lower concentrations of 5-HT. Granisetron produced a small reduction in the response to 5-methoxytryptamine. Tetrodotoxin (TTX) (3 x 10(-7) mol/l) almost abolished the response to 5-methoxytryptamine and markedly suppressed the response to 2-methyl-5-HT, but the responses to 5-HT were only partially reduced. The 5-HT1 antagonist, methiothepin (10(-6) mol/l) depressed the response to 5-HT (10(-7) to 10(-4) mol/l) and blocked its TTX insensitive component. The 5-HT2 antagonist, ketanserin, in concentrations up to 10(-5) mol/l, had no effect on the contractions evoked by 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)