Ca²⁺ channel ligand activities in uterine smooth muscle: Influence of hormonal status

The effects of estrogen and progesterone domination, achieved by administering estrogen (E) and estrogen plus progesterone (E + P), on rat uterine reactivity to Ca²⁺ and to Ca²⁺ channel ligands (antagonist and activator) were compared. The inhibitory activities of nifedipine, diltiazem, and D 600 against K⁺ depolarization-induced responses were not significantly different between E- and E + P-dominated states in longitudinal or circular muscle preparations. Tonic responses were significantly more sensitive than phasic responses, but the rank orders of activity for a series of 14 antagonists were identical, suggesting the existence of a common structure-activity relationship which paralleled that seen previously in other smooth muscles. E + P-dominated uteri were slightly more sensitive to Ca²⁺ responses in K⁺ depolarizing media, but pA₂ values for nifedipine, diltiazem, and D 600 inhibition were not significantly different in tissues from animals in either hormone-dominated state. Binding of [³H]nitrendipine did not differ between hormonal states. Responses to Bay K 8644 were larger in E + P-dominated uteri but the binding density was twofold greater in the E-dominated uterus. This study suggests that pathways of Ca²⁺ mobilization through potential-dependent Ca²⁺ channels in rat uterus are not significantly altered between E- and E + P-dominated environments.