Role of the Na(+)-Ca2+ and Na(+)-H+ antiporters in prolactin release from anterior pituitary cells in primary culture.

2',4'-dimethylbenzamilamiloride (DMB), a somewhat selective inhibitor of the Na(+)-Ca2+ exchanger, in concentrations of 10, 30 and 100 microM did not produce any significant effect on baseline prolactin release from anterior pituitary cells in primary culture. When prolactin secretion was stimulated by the inhibitor of the Na(+)-K(+)-ATPase, ouabain, that activates the Na(+)-Ca2+ exchanger as a Ca(2+)-influx pathway, DMB was able to produce inhibition of prolactin secretion. 5-(N,N-hexamethylene) amiloride (HMA), another amiloride analog which specifically inhibits the Na(+)-H+ antiporter and has no inhibitory activity on the Na(+)-Ca2+ exchanger, at the concentrations of 0.1, 1 and 10 microM, did not affect basal prolactin release whereas it significantly reduced prolactin release stimulated by thyrotropin releasing hormone (TRH) (1 microM). These results suggest that the Na(+)-Ca2+ antiporter is involved in the process of prolactin release elicited by the inhibition of the Na(+)-K(+)-ATPase whereas the Na(+)-H+ antiporter is involved in the prolactin secretion elicited by TRH.