Change in Intracellular Cyclic Nucleotide Content Accompanies Relaxation of the Isolated Canine Internal Anal Sphincter

Changes in cyclic nucleotide content arc associated with relaxation of lower esophageal sphincter (LES) smooth muscle. Although agents that increase cyclic AMP (cAMP) or cyclic CMP (cGMP) can relax the LES, relaxation produced by activation of enteric neurons is associated with, an increase in intracellular cGMP. To evaluate these changes in another sphincteric area of the gut, ice determined the effects of electrical field stimulation (EFS) (65 V, I ms) and of several relaxant agents that alter cyclic nucleotide content in isolated strips of canine internal anal sphincter. Each strip was contracted with norepinephrine (3 μM). During maximum contraction, tissues were relaxed by EFS or by addition of relaxant agents. EFS produced, a frequency-related relaxation, accompanied by a significant, increase, in cGMP; however, cAMP increased only slightly at the maximum frequency tested (8 Hz). Both EFS-induced relaxation and increased cGMP content were blocked 1 μM tetrodotoxin. Cumulative addition of sodium nitroprusside, forskolin, 8-bromoguanosine 3',5'-cylic monophosphate, or 8-bromoadenosine 3',5'-cyclic monophosphate relaxed the internal anal sphincter in a concentration-dependent manner. Sodium nitroprusside-induced relaxations were accompanied by concentration-dependent increases in cGMP content, whereas forskolin-induced relaxations were accompanied by concentration-dependent increases in cAMP content. In conclusion, both cAMP and cCMP appear to be intracellular mediators of relaxation in the canine internal anal sphincter. In addition, relaxation produced by activation of intrinsic inhibitory neurons is associated with an elevation of intracellular cGMP. Together with our previous findings in the LES, these results suggest that cCMP may be the intracellular mediator of neuronally induced, relaxation of gut sphincteric regions.