5-HT4 RECEPTORS IN RAT BUT NOT GUINEA-PIG, RABBIT OR DOG ESOPHAGEAL SMOOTH-MUSCLE

1. Marked heterogeneity among species exists in the esophageal respons e to pharmacological agents. The present study compared the response t o serotonin in esophagus from the rat, guinea pig, rabbit and dog. 2. The esophagus from all four species contracted to carbamylcholine and to PGF(2) alpha; responses to serotonin were the most variable among s pecies. 3. Serotonin contracted the guinea pig and rabbit esophagus; a n effect blocked by LY53857 (10(-7)M) and ketanserin (10(-7)M), consis tent with 5-HT2 receptor activation mediating this contraction. 4. Ser otonin neither contracted nor relaxed the canine esophagus and relaxed the rat esophagus via 5-HT4 receptor activation as determined by anta gonism with ICS 205-930 (-log K-B = 6.4), metoclopramide (-log K-B = 6 .7) and its ester congener SDZ 205-557 (-log K-B = 7.9). Two methylene homologs of SDZ 205-557 also had high 5-HT4 receptor affinity (-log K -B = 7.7). 5. Thus, in guinea pig and rabbit esophagus, serotonin indu ced a contraction mediated by 5-HT4 receptors; and serotonin neither c ontracted nor relaxed the canine esophagus. In rat esophagus, serotoni n induced a relaxation mediated by activation of 5-HT4 receptors.