Kazumasa Shimizu, Taeko Ichikawa, Norimoto Urakawa and Shinjiro Nakajyo
Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University,
7-1 Kyonan-cho 1-Chome, Musashino, Tokyo 180-8602, Japan
Abstract: In guinea pig urinary bladder, the hyperosmotic 65╩mM KCl (H-65K+)- or carbachol (CCh)-induced contraction was inhibited by an addition of papaverine in a concentration-dependent manner. The cAMP content of the muscle in the presence of H-65K+ or CCh was increased by papaverine only at the higher concentration of 100╩mM, but cGMP content was not affected by papaverine. Forskolin, compared with papaverine, increased cAMP content in a concentration-dependent manner, and nitroprusside did not significantly increase cGMP content. In a fura╩2 loaded muscle, papaverine did not affect an increase of [Ca2+]i level by high K+ or CCh. The increase of oxidized flavoprotein (FPox) fluorescence and muscle contraction in the presence of H-65K+ or CCh was decreased by papaverine (1-100╩mM), and the increase of pyridine nucleotide (PNred) fluorescence was not affected by papaverine. In summary, it was concluded that papaverine induced relaxation by inhibiting mitochondrial respiration in guinea pig urinary bladder as well as ileum. Moreover, it is proposed that the mechanism of papaverine-induced relaxation in the smooth muscle, which shows predominantly a metabolic dependency on its contraction, is an inhibition of mitochondrial respiration.
Keywords: Metabolic inhibition, Guinea pig urinary bladder, Papaverine, Muscle relaxation