Adrenoceptor subtype involvement in suppression of prolactin secretion by noradrenaline

In sheep, injection of noradrenaline suppresses prolactin secretion by a direct effect at the pituitary gland. The aims of this study were to use primary 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 acts as a prolactin release-inhibiting factor (PIF). Noradrenaline and dopamine suppressed prolactin secretion from ovine pituitary cells with ED50s of 60.9+/-46.6 and 1.5+/-1.0x10-9 mol/l, respectively (P<0.05). The in-vitro prolactin release-inhibiting effect of noradrenaline (10-7 mol/l) was not blocked by the dopamine antagonists pimozide (D2) or SCH23390 (D1) but was blocked by each of the adrenoceptor antagonists (alpha1-adrenoceptor antagonists prazosin and WB4101, the alpha2-adrenoceptor antagonist yohimbine and the beta-adrenoceptor antagonist propranolol). The response to adrenoceptor agonists was also tested in vitro. The alpha1-adrenoceptor agonists phenylephrine and cirazoline significantly suppressed prolactin. Of the alpha2-agonists, clonidine had no effect whereas oxymetazoline and p-aminoclonidine both suppressed prolactin. The beta-adrenoceptor agonist isoproterenol also suppressed prolactin while the specific beta3-antagonist BRL37344 had no effect. When the adrenoceptor antagonists were tested in vivo in ewes manipulated to be in the luteal phase, only WB4101 significantly (P<0.05) increased plasma prolactin concentrations but this response was small and only observed in one of two experiments. In summary, these experiments 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 experiments do not provide convincing evidence for a role for noradrenaline as a physiologically important PIF.