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.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D007473:Ion Channels / Q000378:metabolism*; D008024:Ligands / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D009568:Nitrendipine / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D002121:Calcium Channel Blockers; D004967:Estrogens; D007473:Ion Channels; D008024:Ligands; D011374:Progesterone; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009568:Nitrendipine; D011188:Potassium; D002118:Calcium