title: The influence of the calcium antagonist fendiline on tone and motility of the guinea pig gut smooth muscle and the cAMP and cGMP concentrations of the isolated terminal ileum.
abstract: In various parts of the guinea pig gastrointestinal tract the calcium antagonist N-(2-benzhydryl-ethyl)-N-(1-phenyl-ethyl)-amine hydrochloride (fendiline, Sensit) decreases the smooth muscle tone elevated by K+-induced depolarisation. This effect is antagonized by addition of extra-Ca++. The muscle relaxation is dos-dependent and amounts to 45-90% after 1-5 microng/ml fendiline. Proportionally to this effect the tissue concentration in cGMP is decreased whereas cAMP remains unchanged. After 54 micron/ml theophylline the cAMP level in the terminal ileum is increased significantly whereas cGMP does not change. Theophylline has no influence on the relaxing effect of 1 microng/ml fendiline. By contrast, the increase in cAMP after theophylline is prevented by fendiline. These findings are explained by the antagonistic effect of fendiline to Ca++, which activates the guanylate cyclase and inhibits the adenylate cyclase. Furthermore, fendiline seems to prevent the binding of theophylline to guinea pig ileal phosphodiesterase. It is discussed that cGMP plays a physiological role in controlling the intestinal smolth muscle tone and motility.
mesh_terms: D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors*; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004064:Digestive System / Q000187:drug effects; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D010627:Phenethylamines / Q000494:pharmacology*; D013806:Theophylline / Q000037:antagonists & inhibitors
chemical_list: D010627:Phenethylamines; D013806:Theophylline; D000242:Cyclic AMP; D006152:Cyclic GMP; D002118:Calcium