The effects of serotonin (5-HT) on twitch contractions induced by electrical stimulation of guinea-pig common bile duct.

In guinea-pig common bile duct serotonin (5-HT) (10(-7)-10(-5) M) administered cumulatively caused dose-dependent inhibition of the twitches evoked by electrical field stimulation (0.3 ms, 0.1 Hz, supramaximal voltage). Maximum inhibition was 86 +/- 2% of the control twitch amplitude. The effect was mainly due to a presynaptic mechanism since acetylcholine induced contractions were not influenced by 5-HT. This inhibitory action was unaffected by ketanserin (10(-6) M), ICS 205-930 (10(-6) M) and yohimbine (10(-6) M) indicating the lack of involvement of 5-HT2, 5-HT3 and alpha-2 adrenergic receptors respectively. Metoclopramide (3 x 10(-6)-3 x 10(-5) M) per se increased the twitch height and antagonized the 5-HT effect in a non-competitive manner. Methysergide (10(-7)-10(-5) M) also prevented the twitch inhibition and the mode of blockade was not consistent with simple competitive antagonism. The results suggest that presynaptically located 5-HT receptor differs in its pharmacological properties from other neuronal 5-HT receptors.