Kilbinger_1992_Naunyn.Schmiedebergs.Arch.Pharmacol_345_270

The effects of 5-methoxytryptamine and 5-hydroxytryptamine (5-HT) on both basal and electrically evoked outflow of tritium were studied in guinea-pig myenteric plexus preparations preincubated with [3H]-choline. Basal outflow. 5-Methoxytryptamine caused a transient and calcium-dependent increase in basal outflow of [3H]acetylcholine that was abolished by tetrodotoxin. Ondansetron (1 mumol/l) did not affect the stimulatory response of 5-methoxytryptamine but ICS 205-930 (1 and 3 mumol/l) produced parallel rightward displacements of the concentration-response curve to 5-methoxytryptamine. The pKB value for ICS 205-930 was 6.6 suggesting an involvement of 5-HT4 receptors. 5-HT caused an increase in basal outflow of [3H]acetylcholine and a biphasic concentration-response curve was obtained. The maximal response of the first phase to 5-HT (release of 0.98% of tissue tritium) and the maximal response to 5-methoxytryptamine (0.94% of tissue tritium) were similar but 5-methoxytryptamine (-log EC50: 6.9) was less potent than 5-HT (-log EC50 of the high affinity component: 7.9). ICS 205-930 (0.01-1.0 mumol/l) acted as a competitive antagonist against the low affinity component of the 5-HT concentration-response curve with a pA2 value of 8.0. It is concluded that stimulation of both 5-HT4 receptors (by 5-methoxytryptamine and submicromolar concentrations of 5-HT) and 5-HT3 receptors (by micromolar concentrations of 5-HT) causes a release of acetylcholine which in turn leads to smooth muscle contraction. Electrically evoked outflow. This outflow of [3H]-acetylcholine was concentration-dependently inhibited by both 5-methoxytryptamine and 5-HT.