Differences in relaxant effects of cyclic GMP on skinned muscle preparations from the proximal and distal colon of rats

Abstract

The relationship between the intracellular cyclic GMP content and relaxation of smooth muscle was studied in preparations from the proximal and distal colon of rats. Nitric oxide increased the cyclic GMP content of longitudinal muscle of both preparations to approximately the same extents. However, although nitric oxide at 0.03-10 microM induced concentration-dependent relaxation of the proximal segments, it did not induce any significant relaxation of the distal segments. The longitudinal muscle preparations were permeabilized by treatment with alpha-toxin to examine the relaxant effects of cyclic GMP on the contractile elements. Ca2+ induced contraction of the permeabilized muscle, the contraction consisting of a transient and subsequent tonic phases. Cyclic GMP (3-100 microM) reversed the tonic contractions induced by various Ca2+ concentrations (1-30 microM). The magnitude of the relaxant effect of cyclic GMP was significantly more in the proximal region than in the distal region. But in contrast to nitric oxide, cyclic GMP induced slight, but clear relaxation of the distal colon. The inhibitory effects of cyclic GMP on phasic contraction, like those on tonic contraction, were high in the proximal region and low in the distal region. These results suggest that the difference in the relaxant effects of nitric oxide in the proximal and distal longitudinal muscles is not due to a difference in extents of cyclic GMP generation, but mainly to a difference in the sensitivities of the contractile elements in the two regions to cyclic GMP.