Inhibitory Mechanism of Papaverine on the Smooth Muscle of Guinea Pig Urinary Bladder

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 100μM, 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(1−100μM), 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.