DIFFERENCES IN RELAXANT EFFECTS OF CYCLIC-GMP ON SKINNED MUSCLE PREPARATIONS FROM THE PROXIMAL AND DISTAL COLON OF RATS

The relationship between the intracellular cyclic GMP content and rela xation of smooth muscle was studied in preparations from the proximal and distal colon of rats. Nitric oxide increased the cyclic GMP conten t of longitudinal muscle of both preparations to approximately the sam e extents. However, although nitric oxide at 0.03-10 mu M induced conc entration-dependent relaxation of the proximal segments, it did not in duce any significant relaxation of the distal segments. The longitudin al muscle preparations were permeabilized by treatment with alpha-toxi n to examine the relaxant effects of cyclic GMP on the contractile ele ments. Ca2+ induced contraction of the permeabilized muscle, the contr action consisting of a transient and subsequent tonic phases. Cyclic G MP (3-100 mu M) reversed the tonic contractions induced by various Ca2 + concentrations (1-30 mu M). The magnitude of the relaxant effect of cyclic GMP was significantly more in the proximal region than in the d istal region. But in contrast to nitric oxide, cyclic GMP induced slig ht, but clear relaxation of the distal colon. The inhibitory effects o f cyclic GMP on phasic contraction, like those on tonic contraction, w ere high in the proximal region and low in the distal region. These re sults suggest that the difference in the relaxant effects of nitric ox ide in the proximal and distal longitudinal muscles is not due to a di fference in extents of cyclic GMP generation, but mainly to a differen ce in the sensitivities of the contractile elements in the two regions to cyclic GMP.