Characterization of the contractile response induced by 5-methoxytryptamine in rat stomach fundus strips

This study examined effects of 5-methoxytryptamine (5-MOT), an agonist at 5-HT4 and 5-HT2B receptors, on the contractile response and acetylcholine release in rat stomach fundus strips. 5-MOT (10(-9)-10(-5) M) produced a concentration-dependent increase in the contraction, while it evoked acetylcholine release in a 'bell-shaped' concentration-dependent manner. Atropine reduced 5-MOT (10(-8)-10(-6) M)-induced contractions, but it had little effect on the contractions evoked by higher concentrations. 5-MOT-induced contraction and acetylcholine release were inhibited by SDZ 205-557 (2-methoxy-4-amino-5-chloro-benzoic acid 2-[diethylamino] ethyl ester), a 5-HT4 receptor antagonist. In the presence of atropine, both SDZ 205-557 and yohimbine, a 5-HT2B receptor antagonist, inhibited the contraction. In the presence of tetrodotoxin, the contraction was inhibited by yohimbine, but not by SDZ 205-557. These results suggest that the contractile action of 5-MOT in rat stomach fundus involves atropine-sensitive and atropine-resistant components. The sensitive contraction appears to be mediated through 5-HT4 receptors located on cholinergic neurons, whereas the resistant contraction is mediated through 5-HT4 receptors located on non-cholinergic neurons and through 5-HT2B receptors.