Effect of isoproterenol and D-600 on calcium movements in rat myometrium.
The effects of two smooth muscle relaxants, isoproterenol and D-600, on calcium movements in rat myometrium were investigated. Both relaxants caused a nonspecific increase in 45-Ca efflux due to changes in mechanical tension but the additional net loss expected on the basis of previous studies with isoproterenol could not be demonstrated due to a high background of calcium exchange. Analysis of 45-Ca and 40-Ca residual in the muscle after efflux experiments and washing of the tissue in a Ca-deficient solution containing LaCl3 (2.0 mM) showed that the specific activity ratio 45-Ca/40-Ca was unaltered with isoproterenol and, thus, the net loss of calcium occurred equally from slowly and rapidly exchanging compartments. "Pulse label" experiments in which 45-Ca and either isoproterenol or D-600 were added simultaneously for a 2-minute period demonstrated that both relaxants decreased the 45-Ca space; however, the specific activity ratio 45-Ca/40-Ca in the tissue was reduced while 40-Ca remained unchanged in the presence of D-600. With isoproterenol, the 45-Ca/40-Ca ratio was increased while 40-Ca was reduced. These data support the hypothesis that isoproterenol stimulates a net efflux of calcium whereas D-600 inhibits the influx of calcium. Since previous studies have demonstrated that relaxants which increase cyclic3,5-adenosine monophosphate (cyclic AMP) (isoproterenol, dibutyryl cyclic AMP and papaverine) produce consistent decreases in tissue Ca but others (D-600) do not, it is concluded that relaxants which increase tissue cyclic AMP stimulate a net efflux of calcium but other antagonists may act by inhibiting calcium influx into rat myometrium.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D003864:Depression, Chemical; D005260:Female; D005711:Gallopamil / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D007811:Lanthanum / Q000494:pharmacology; D009215:Myometrium / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000032:analysis / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D012964:Sodium / Q000032:analysis / Q000378:metabolism; D013268:Stimulation, Chemical; D014599:Uterus / Q000378:metabolism*; D014700:Verapamil / Q000031:analogs & derivatives*
D002132:Calcium Radioisotopes; D005711:Gallopamil; D007811:Lanthanum; D012964:Sodium; D014700:Verapamil; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium