Mechanism of a nitric oxide donor NOR 1-induced relaxation in longitudinalmuscle of rat proximal colon

We previously suggested that nitric oxide (NO)-mediated relaxation of the r at proximal colon is not associated with change in cyclic GMP content. We f urther studied the intracellular mechanism of NO-induced relaxation by meas uring changes in tension and intracellular Ca2+ concentration ([Ca2+](i)), simultaneously. NOR 1, NO donor, relaxed the longitudinal muscle of the rat proximal colon, which was precontracted by carbachol, with a concomitant d ecrease in [Ca2+](i). ODQ, an inhibitor of soluble guanylate cyclase, parti ally inhibited the relaxant effect of only higher concentrations of NOR 1, but Rp-8-Br-cGMPS, an inhibitor of cyclic GMP-dependent protein kinase (PKG ), did not have any effects on the relaxant effect of NOR 1. When the prepa rations were transferred to normal solution after the treatment with thapsi gargin, an inhibitor of sarcoplasmic reticulum (SR) Ca2+-ATPase, in the abs ence of Ca2+, contraction with a concomitant increase in [Ca2+](i) occurred . NOR 1 did not show significant effects on the tension and [Ca2+](i) in th apsigargin-treated preparations. In high K+-precontracted preparations, NOR 1 relaxed the preparations with a slight change in [Ca2+](i). The relaxant effect was significantly inhibited by ODQ and Rp-8-Br-cGMPS. These results suggest that NO induces the relaxation preferentially by acting thapsigarg in-sensitive function of SR and in turn decreasing [Ca2+](i), although a cy clic GMP-PKG pathway is suggested under the experimental conditions of a hi gh K+ concentration.