Cyclic Nucleotides Increase During Neuronally Induced Relaxation of Sphincteric and Nonsphincteric Gastrointestinal Smooth Muscle

Abstract

Neuronal stimulation of most isolated precontracted gastrointestinal smooth muscle results in relaxation. This study examined the changes in cyclic nucleotide content associated with neuronally induced relaxation in sphincteric and nonsphincteric smooth muscle of the gut. Electrical field stimulation produced a frequency‐dependent relaxation of the guinea pig proximal colon (EF50= 1.6 Hz) and taenia coli (EF50= 2.4 HZ), and the canine proximal colon (EF50= 3.1 Hz) and internal anal sphincter (EF50= 3.0 Hz). Changes in cyclic nucleotide content occurred during EFS‐induced relaxation. Cyclic AMP levels were significantly increased in the guinea pig poximal colon and taenia coli and in the canine proximal colon. No change in cyclic GMP occurred in these smooth muscles. Conversely, in the canine internal anal sphincter the cyclic GMP content increased significantly with no change in cyclic AMP. These effects in this sphincter are similar to those identified previously in the lower esophageal sphincter of opossum, dog, and man. Tetrodotoxin blocked the EFS‐induced relaxation and the associated accumulation of cyclic nucleotides of all tissues. Therefore, EFS‐induced relaxation is mediated by the activation of neurons and the release of inhibitory neurotransmitter(s). Also, EFS‐induced relaxation is closely associated with increases in smooth muscle cyclic nucleotide content. Most importantly, the change in cyclic nucleotide accumulation that occurs during EFS‐induced relaxation is different for sphincteric and nonsphincteric smooth muscle, (i.e., different cyclic nucleotides are generated in sphincteric and nonsphincteric smooth muscle in response to stimulation of nonadrenergic, nonchohnergic, inhibitory enteric neurons).