The possible role of calmodulin in the inhibition of prolactin secretion by dopaminergic antagonists.
Several previous reports have indicated that a number of dopaminergic antagonists paradoxically inhibit prolactin secretion at micromolar concentrations. It is well known that some of these drugs, including pimozide and the phenothiazines, are inhibitors of calmodulin activity. Here we report that micromolar concentrations of several dopaminergic antagonists inhibit prolactin secretion from isolated rat anterior pituitary cells and calmodulin activity (calmodulin-activated cyclic GMP phosphodiesterase). Inhibition of calmodulin activity may thus, at least partially, explain the inhibitory effect of these drugs on prolactin secretion.
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002478:Cells, Cultured; D004294:Domperidone / Q000494:pharmacology; D018492:Dopamine Antagonists; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D018492:Dopamine Antagonists; D004294:Domperidone; D011388:Prolactin; D015106:3',5'-Cyclic-GMP Phosphodiesterases