saralasin and calmidazolium

Renin and angiotensin II (AII) have been demonstrated in the mammalian central nervous system, and AII has been found to promote PRL release in the rat and monkey. We added AII to monolayer cultures of human anterior pituitary cells and found significant PRL release by 30 min with concentrations of AII as low as 10(-10) M. This AII-induced PRL release was inhibited by the specific AII antagonist saralasin. AII-induced PRL release was a calcium-dependent process, since the calcium channel blockers verapamil and nifedipine as well as the calcium-calmodulin antagonist R2471 significantly inhibited AII-induced PRL release. Prostaglandins E2, A2, and F2 alpha also inhibited AII-induced PRL release. The significance of this latter observation is not clear, however, as indomethacin, an inhibitor of the cyclo-oxygenase prostaglandin metabolic pathway, had no effect on AII-induced PRL release. In light of recent immunohistochemical evidence of the presence of renin, angiotensinogen, and converting enzyme in human lactotrophs, our data support the concept that AII may be an important autocrine regulator of PRL secretion.

Topics: Adult; Angiotensin II; Calcium; Calmodulin; Cells, Cultured; Humans; Imidazoles; Male; Middle Aged; Nifedipine; Pituitary Gland, Anterior; Prolactin; Prostaglandins; Saralasin; Verapamil