Mechanism of relaxant response to papaverine on the smooth muscle of non-pregnant rat uterus.
In the present paper, we examined a mechanism of the papaverine induced relaxation in the smooth muscle of non-pregnant rat uterus. The hyperosmotic 65 mM KCl (H-65K+)-or oxytocin-induced contraction in the uterus was inhibited by an addition of papaverine in a concentration-dependent manner. Papaverine did not increase both cAMP and cGMP contents in the uterus in the presence of H-65K+ or oxytocin. In fura 2 loaded muscles, papaverine did not affect an increase of [Ca2+]i level by high K+ or oxytocin. In permeabilized muscles, papaverine had no effect on the Ca2+-induced contraction. H-65K+ and oxytocin increased the rate of oxygen consumption 1.8 and 1.5 times higher than that in the resting condition, respectively. The increase of oxygen consumption in the H-65K+ or oxytocin was significantly inhibited by papaverine (1-100 microM). These results suggested that papaverine inhibits smooth muscle contraction mainly by inhibition of mitochondrial respiration in rat uterus as well as guinea pig ileum, which shows a highly spontaneous activity and a highly metabolic dependency of a contraction.
Shimizu
K
K
Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University, Tokyo, Japan.
Yoshihara
E
E
Takahashi
M
M
Gotoh
K
K
Orita
S
S
Urakawa
N
N
Nakajyo
S
S
D000818:Animals; D002118:Calcium / Q000032:analysis; D000242:Cyclic AMP / Q000032:analysis; D006152:Cyclic GMP / Q000032:analysis; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010121:Oxytocin / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000187:drug effects*
D010121:Oxytocin; D010208:Papaverine; D000242:Cyclic AMP; D006152:Cyclic GMP; D002118:Calcium