Physiological concentrations of dopamine decrease adenosine 3',5'-monophosphate levels in cultured rat anterior pituitary cells and enriched populations of lactotrophs: evidence for a causal relationship to inhibition of prolactin release.

Abstract

The possible involvement of cAMP in mediating the dopaminergic inhibition of PRL release was studied in primary cultures of anterior pituitary cells from female rats and in lactotroph-enriched subpopulations. In the presence of the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX), dopamine (DA) depressed cAMP accumulation in a concentrationdependent fashion between 1–100 nM. The effect was significant within less than 1 min and maximal after about 10 min. Inhibition of PRL release by DA occurred at similar concentrations and paralleled the time course of inhibition of cAMP levels. The DA agonist apomorphine also inhibited cAMP levels and PRL release at nanomolar concentrations and acted as a full agonist, whereas the a-adrenoceptor agonist phenylephrine had no effect at 1 μM. The DA receptor blockers spiperone, domperidone, pimozide, Z-sulpiride, and flupentixol reversed the DA-induced inhibition of cAMP accumulation with a rank order of potency comparable to that of reversing DA-induced inhibiti...