Dopaminergic inhibition of ionophore A23187-stimulated release of prolactin from rat anterior pituitary cells.

Abstract

The divalent cation ionophore A23187 stimulated release of prolactin from primary cultures of rat anterior pituitary cells. The stimulation required Ca”, since the omission of Ca2+ or the presence of ethylene glycol bisw-aminoethyl ether)N,Np,W-tetraacetic acid inhibited the stimulation. Near-maximal stimulation was obtained with 5 PM A23187 for 10 min. The A23187stimulated release of prolactin was inhibited by preincubating cells for 1 h with 2-Br-a-ergocryptine (bromocriptine), a dopaminergic agonist. The half-maximal inhibition occurred at about 0.5 m and complete inhibition was observed at 3 m. Dopamine and dihydroergocryptine, another dopaminergic agonist, also inhibited the A23187 stimulation. d-Butaclamol and cis(Z)-flupenthixol, dopaminergic antagonists, blocked the bromocriptine inhibition, which suggested that the inhibition was caused by bromocriptine acting on the dopamine receptor. The A23187-stimulated release of prolactin from GH cells, a pituitary tumor cell line that lacks detectable dopamine receptors, was not inhibited by bromocriptine. Cycloheximide did not affect the bromocriptine inhibition, which suggested that protein synthesis is not required. Uptake of 46Ca2’ in the presence and absence of A23187 was not affected by bromocriptine. These data indicate that dopaminergic agonists inhibit prolactin release at a step after Ca2’ uptake.