On the nature of the receptor mediating the action of 5-hydroxytryptamine in potentiating responses of the mouse urinary bladder strip to electrical stimulation.

Superfused mouse bladder strip responded to electrical stimulation (ES) by twitch contractions. These contractions were potentiated by 5-hydroxytryptamine (5-HT; 0.03-3.0 microM). Three tryptamine analogues were tested for their ability to potentiate the responses to ES and their relative activities were compared with values in the literature. 5-Carboxamidotryptamine was more potent than 5-HT, N-omega-methyl 5-HT was about equipotent, and alpha-methyl 5-HT was much less potent. Exogenous noradrenaline did not reduce the effect of 5-HT, although it reduced the response of the tissue to ES. The maximum increase in tissue tension evoked by 5-HT was unaltered by phentolamine (1 microM) or bretylium (25 microM). These results show that 5-HT did not act on the bladder by inhibiting the release of catecholamines from intrinsic nerves. The effect of 5-HT proved very resistant to attempts to block it with conventional 5-HT antagonists. Several antagonists were studied including ketanserin, methysergide, methiothepin, and MDL 72222 but even at concentrations as high as 1 microM none of them exhibited any marked inhibitory effect against the action of 5-HT. At 10 microM some compounds showed activity, but none abolished the effect except methiothepin - and its action was not surmountable by increasing the concentration of 5-HT. Thus the effect of 5-HT on the bladder was not mediated by 5-HT receptors of types 'M', 'D' or 5-HT2.(ABSTRACT TRUNCATED AT 250 WORDS)