The binding sites of the calcium antagonist [3H] PN 200,110 in the human myometrium and myosalpinx.
Calcium antagonists of the dihydropyridine type may prove to be an important adjunct to the therapy of premature labor due to their proven ability to inhibit uterine contractility. Specific binding sites for calcium blockers were concentrated in 45,000 X g membrane preparations of human myometrium and myosalpinx. Scatchard plot analysis of the binding of [3H] PN 200,110, a benzoxadiazole-substituted dihydropyridine derivate, revealed that the binding sites of myometrial membranes numbered between 500 and 700 fmoles/mg protein (Bmax) and had an affinity (KD) of 0.3 +/- 0.1 nmol/l. In myosalpingeal membrane preparations Bmax was between 250 and 300 fmoles/mg protein, with KD values of 0.9 +/- 0.1 nmol/l. Unlabelled calcium antagonists displaced [3H] PN 200,110 binding in the following order of potency ranking: nitrendipine greater than or equal to nifedipine greater than d-cis-diltiazem greater than D-600 greater than or equal to tiapamil. The calcium channels were especially dense (796 +/- 186 fmoles/mg protein) in the myometrium of the dorsal uterine wall. The number of binding sites in the myosalpinx was greatest in the isthmus (242 +/- 23 fmoles/mg protein).
D000328:Adult; D000368:Aged; D002121:Calcium Channel Blockers / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D017275:Isradipine; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism*; D009215:Myometrium / Q000378:metabolism*; D010069:Oxadiazoles / Q000378:metabolism* / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000378:metabolism*
D002121:Calcium Channel Blockers; D010069:Oxadiazoles; D017275:Isradipine