Calmodulin inhibitors and 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate do not prevent the inhibitory effect of prostaglandin F2α on cyclic AMP production in isolated rat corpora lutea

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Abstract
In the rat corpus luteum, prostaglandin F2α (PGF2α) 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 PGF2α 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 μg/ml), PGF2α (10 μmol/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 μmol/l), did not abolish the effect of PGF2α. Similarly ineffective was the combination of TMB-8 (150 μmol/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 μmol/l, did not interfere with the inhibitory effect of PGF2α on cAMP, while suppressing (at 300 μmol/l) progesterone secretion in LH-treated tissue. Furthermore, inhibition by PGF2α was not impaired by pimozide, a diphenylbutylpiperidine (25 and 50 μmol/l) nor by N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide (W-7; 15 and 45 μmol/l). In the presence of LH alone, W-7 (45 μmol/l) inhibited and TMB-8 (30 μmol/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 PGF2α on luteal cAMP production. J. Endocr. (1987) 113, 205–212

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