Recent findings suggest that nonadrenergic inhibitory responses of the smooth muscle of the gastrointestinal tract is mediated by nitric oxide and some intestinal peptides including VIP, PACAP and CGRP. Although nitric oxide was suggested to mediate the nonadrenergic relaxation in various regions of gastrointestinal tracts of many species, further careful studies revealed that nitric oxide participates in the relaxation in restricted regions, not throughout the tract. It was also found that the peptides work in extremely restricted regions of the tract. Importance of the role of nitric oxide in the relaxation varies with different regions, strains and species. Moreover, it significantly decreases with the age of the rat, especially between 4-8 weeks of age. Inhibitors of Ca2+-activated K+ channels inhibited the relaxation in almost all regions examined in rats, although the magnitude of the inihibition varied from region to region. The intracellular action mechanism(s) of nitric oxide was discussed in relation to changes in cyclic GMP level, intracellular Ca2+ level and membrane potentials of the smooth muscle cells.
