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.