Dopaminergic receptors in the anterior pituitary gland. Correlation of [3H]dihydroergocryptine binding with the dopaminergic control of prolactin release.

Abstract

The ergot alkaloid [“Hldihydroergocryptine, a potent dopaminergic agonist, has been used to study binding sites in bovine anterior pituitary membranes. One function of the anterior pituitary gland, prolactin secretion, as we show is under typical dopaminergic control and was measured in uitro in another series of experiments using rat anterior pituitary cells in primary culture in order to establish a correlation between binding and a biological function. The dopaminergic specificity of ligand binding and the biological process was demonstrated by the fact that agonists competed for [“Hldihydroergocryptine binding and inhibited prolactin release with an identical order of potency: apormorphine > dopamine > epinephrine 2 norepinephrine >> isoproterenol. Ergot alkaloids, which behave as agonists in this system, potently inhibited prolactin release from pituitary cells to about the same extent as dopamine (80 to 90% of basal levels) and were potent competitors of [“Hldihydroergocryptine binding (K,, 0.2 to 0.5 4. Dopaminergic antagonists competed for [“HIdihydroergocryptine binding in bovine anterior pituitary membranes in parallel to their ability to reverse either dopamine or dihydroergocornine inhibition of prolactin release from rat anterior pituitary cells. [3HlDihydroergocryptine binding fulfilled another criterion of specific receptor sites in that binding to the anterior pituitary sites was saturable with an apparent dissociation constant (K,) of 2.2 + 0.6 nu and a mean saturation value of 0.32 + 0.02 pmol/mg of protein. The close correlation which exists between the properties