Calmodulin inhibitors and 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate do not prevent the inhibitory effect of prostaglandin F2 alpha on cyclic AMP production in isolated rat corpora lutea.
In the rat corpus luteum, prostaglandin F2 alpha (PGF2 alpha) rapidly inhibits LH-induced cyclic AMP (cAMP) production when given in vivo or to isolated corpora lutea, but not to broken-cell preparations. The suggestion that increased cytosolic calcium concentration mediates PGF2 alpha action was investigated in corpora lutea of pseudopregnancy induced in immature rats by administration of pregnant mare serum gonadotrophin (15 i.u.). Isolated 10-day-old corpora lutea were incubated for 90 min with LH (5 micrograms/ml), PGF2 alpha (10 mumol/l) and other additions, and cAMP concentration in the tissue was estimated. The putative inhibitor of intracellular calcium release or action, 8-(n,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8; 30 or 150 mumol/l), did not abolish the effect of PGF2 alpha. Similarly ineffective was the combination of TMB-8 (150 mumol/l) and calcium-depleted medium (free ionized calcium concentration, 30 nmol/l). Calmodulin inhibitors of three different chemical structures were then tested. The phenothiazine trifluoperazine, at 300 as well as 30 mumol/l, did not interfere with the inhibitory effect of PGF2 alpha on cAMP, while suppressing (at 300 mumol/l) progesterone secretion in LH-treated tissue. Furthermore, inhibition by PGF2 alpha was not impaired by pimozide, a diphenylbutylpiperidine (25 and 50 mumol/l) nor by N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide (W-7; 15 and 45 mumol/l). In the presence of LH alone, W-7 (45 mumol/l) inhibited and TMB-8 (30 mumol/l augmented cAMP accumulation, indicating that the luteal tissue was effectively exposed to these compounds. Thus, drugs known to inhibit calcium- and calmodulin-dependent processes in a variety of tissues did not abolish the inhibitory action of PGF2 alpha on luteal cAMP production.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003338:Corpus Luteum / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D003864:Depression, Chemical; D015237:Dinoprost; D005260:Female; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D002147:Calmodulin; D011460:Prostaglandins F; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D007986:Luteinizing Hormone; D015237:Dinoprost; D000242:Cyclic AMP; D002118:Calcium