IDENTIFICATION OF A D1-DOPAMINE RECEPTOR, NOT LINKED TO ADENYLATE-CYCLASE, ON LACTOTROPH CELLS

1 We studied the lactotroph cells of the rat by both in vivo and in vitro pharmacological techniques for the presence of D1-receptors. Both approaches revealed the presence of a D2-receptor, stimulated by quinpirole (resulting in an inhibition of prolactin secretion) and blocked by domperidone. 2 Administration of fenoldopam, the most selective D1-receptor agonist currently available, resulted in a dose-dependent decrease of prolactin secretion in vivo (after pretreatment with alpha-methyl-p-tyrosine) and in vitro (cultured pituitary cells). This increase was dose-dependently blocked by the selective D1-receptor antagonist, SCH 23390, and although the effect of fenoldopam was less than that obtained by D2-receptor stimulation, these data suggest that a D1-receptor also controls prolactin secretion. 3 In order to detect the location of these dopamine receptors, autoradiographic studies were performed by use of [H-3]-SCH 23390 and [H-3]-spiperone as markers for D1- and D2-receptors, respectively. Specific binding sites for [H-3]-SCH 23390 were demonstrated. Fenoldopam dose-dependently reduced [H-3]-SCH 23390 binding, but had no effect on [H-3]-spiperone binding. Immunocytochemical labelling of prolactin cells after incubation with [H-3]-SCH 23390 revealed that the granulae and hence, D1 binding sites were present on the lactotroph cells. 4 Radioligand binding studies performed on membranes from anterior pituitary cells revealed the presence of the D2-receptor (54 fmol mg-1 protein) with a K(d) of 0.58 nM for [H-3]-spiperone, but failed to detect D1-receptors. 5 Finally, we studied the effect of dopamine and of fenoldopam on the adenosine 3':5'-cyclic monophosphate (cyclic AMP) content of anterior pituitary cells. Although cyclic AMP increased upon prostacyclin administration, indicating an intact adenylate cyclase system, fenoldopam failed to increase the cyclic AMP production. 6 It is tempting to speculate that fenoldopam reduces prolactin secretion through interaction with a non-cyclase-linked D1-receptor on the lactotroph cells.