Influence of 5‐hydroxytryptamine and the effect of a new serotonin receptor antagonist (sarpogrelate) on detrusor smooth muscle of streptozotocin‐induced diabetes mellitus in the rat *

BACKGROUND: We evaluated the changes in the response of detrusor muscle to 5-hydroxytryptamine (5-HT; serotonin) and its receptor mechanisms in pathologic bladder of diabetes mellitus rats. METHODS: Eight-week-old male Wistar rats were given an intraperitoneal injection of streptozotocin (STZ, 60 mg/kg) in order to induce diabetes mellitus (4 weeks' duration). The bladder strips (10 x 2 mm) were subjected to a tension of 1.0 g in organ baths for the measurements of isotonic contractile responses to 5-HT or relaxation responses to 5-HT antagonists. RESULTS: Bladder strips from STZ-diabetic rats responded to 5-HT with greater contractions than did those of control rats, given vehicle alone. However, bladder strip weights gradually increased in the STZ-diabetic rats as compared with control rats and when the contractile response to 5-HT was expressed as a percentage of the response to 10(-1) mol/L KCl there was no statistically significant difference between the groups. In both control and diabetic rats, the 5-HT3 selective antagonist did not markedly inhibit the contractile response to 5-HT. In contrast, the 5-HT2A selective antagonist inhibited the contractile response to 5-HT in a dose-dependent manner. CONCLUSIONS: These results suggest that the increased contractile response to 5-HT in diabetic rats' bladder is related to smooth muscle hypertrophy and/or hyperplasia and indicate that this effect is mediated by activation of 5-HT2A receptors.