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ﾊ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ﾊ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ﾊ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ﾊ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