Adrenoceptor subtype involvement in suppression of prolactin secretion by noradrenaline

In sheep, injection of noradrenaline suppresses prolactin secretion by a di rect effect at the pituitary gland. The aims of this study were to use prim ary cultures of ovine pituitary cells to examine the receptor subtypes that mediate the inhibitory effect of noradrenaline on prolactin secretion and, by using receptor antagonists in vivo, determine whether noradrenaline act s as a prolactin release-inhibiting factor (PIF). Noradrenaline and dopamin e suppressed prolactin secretion from ovine pituitary cells with ED50s of 6 0.9 +/- 46.6 and 1.5 +/- 1.0 x 10(-9) mol/l, respectively (P < 0.05). The i n-vitro prolactin release-inhibiting effect of noradrenaline (10(-7) mol/l) was not blocked by the dopamine antagonists pimozide (D-2) or SCH23390 (D- 1) but was blocked by each of the adrenoceptor antagonists (alpha 1-adrenoc eptor antagonists prazosin and WB4101, the alpha 2-adrenoceptor antagonist yohimbine and the beta-adrenoceptor antagonist propranolol). The response t o adrenoceptor agonists was also tested in vitro. The alpha 1-adrenoceptor agonists phenylephrine and cirazoline significantly suppressed prolactin. O f the alpha 2-agonists, clonidine had no effect whereas oxymetazoline and p -aminoclonidine both suppressed prolactin. The beta-adrenoceptor agonist is oproterenol also suppressed prolactin while the specific beta 3-antagonist BRL37344 had no effect. When the adrenoceptor antagonists were tested in vi vo in ewes manipulated to be in the luteal phase, only WB4101 significantly (P<0.05) increased plasma prolactin concentrations but this response was s mall and only observed in one of two experiments. In summary, these experim ents suggest that adrenoceptors and not dopamine receptors are responsible for the inhibitory effect of noradrenaline on prolactin secretion in vitro but do not implicate a particular adrenoceptor subtype. The in-vivo experim ents do not provide convincing evidence for a role for noradrenaline as a p hysiologically important PIF.