IS NITRIC-OXIDE INVOLVED IN 5-HT3 RECEPTOR-MEDIATED NEUROGENIC RELAXATION OF GUINEA-PIG PROXIMAL COLON

The relaxations mediated by the activation of 5-HT receptors in the gu inea pig proximal colon were investigated. Longitudinal strips were cu t from the colon segment and placed into the bath. In the presence of atropine (0.2 mu M), the relaxations were evoked by adding increasing concentrations of 5-HT (1-100 mu M). Noncumulative concentration-respo nse curves were established in the absence and presence of either 5-HT or nitric oxide synthase (NOS) antagonists. Selective 5-HT3 antagonis ts tropisetron (10 and 100 nM) and ondansetron (1 mu M) inhibited the relaxations and shifted the concentration-response curves to the right . Similar effects were observed in the presence of the NOS inhibitor N -G-nitro-L-arginine (3.2, 10, 32 mu M) and partly reversed with L-argi nine (100, 320 mu M). N-G-nitro-D-arginine, serving as a negative cont rol, was ineffective. The relaxations were further inhibited in the pr esence of the soluble guanylate cyclase blocker methylene blue (10 mu M) or NO scavenger hemoglobin (32 mu M). These results suggest that th e 5-HT3 receptor plays a role in neurogenic relaxations of guinea pig proximal colon, which are at least partly mediated via release of NO f rom nerve endings.