Antiphosphodiesterase activity and nonspecific smooth muscle relaxation tested on intestinal smooth muscles.
Mitochondrial, microsomal and soluble fractions separated from the guinea pig taenia and from the dog longitudinal smooth muscle were used as phosphodiesterase preparation. Each preparation had low and high Km values, indicating the existence of at least two kinds of phosphodiesterase. Papaverine and Aspaminol (1, 1-diphenyl-3-piperidinobutanol hydrochloride), hydralazine, caffeine Na benzoate and aminophylline were used at test drugs. Aspaminol had little inhibitory effect on phosphodiesterase. Ki value of papaverine almost equalled the concentration (M) which was necessary to produce 50% relaxation. Relaxation of the guinea pig taenia by papaverine was preceded by an increase of intracellular cyclic AMP,. Therefore, the action of papaverine is likely to be mediated by an increase in cyclic AMP, which is caused by inhibition of the phosphodiesterase-catalyzed breakdown of cyclic AMP. There was little correlation between relaxing activities of the drugs used and their antiphosphodiesterase activities. Relaxation of the smooth muscle induced by the smooth muscle relaxants excepting papaverine is not due to inhibition of phosphodiesterase.
D000818:Animals; D002432:Cecum / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007422:Intestines / Q000187:drug effects* / Q000201:enzymology; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000201:enzymology; D010208:Papaverine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors
D009125:Muscle Relaxants, Central; D010726:Phosphodiesterase Inhibitors; D010208:Papaverine; D000242:Cyclic AMP