Adrenergic and VIP stimulation of cyclic AMP accumulation in ovine pineals

In vitro autoradiography of [125I]cyanopindolol ([125I]cyp) binding to sections of ovine pineal reveals a uniform distribution of beta-adrenergic receptors throughout the gland. Norepinephrine (NE) stimulated cyclic AMP production in pineal slices in both a time- and dose-dependent manner, producing a maximal two-fold increase. NE, isoproterenol (ISO) and epinephrine (E) stimulate cyclic AMP (cAMP) production with equal potency. NE stimulation of cAMP was totally blocked by propranolol (beta antagonist) but only partially blocked by practolol (a beta 1 preferential antagonist) indicating a mixed population of beta 1 and beta 2 receptor subtypes. Displacement of [125I]cyp binding by either practolol or zinterol (preferential beta 2 agonist) revealed IC50s of 1.3 x 10(-5) M and 9.95 x 10(-8) M respectively, confirming a mixed population of beta 1 and beta 2 receptors. A range of peptides previously localised within the pineal by immunocytochemistry were tested at a concentration of 10(-5) M for their effect on cyclic AMP production in pineal homogenates. Only vasoactive intestinal peptide (VIP) was effective showing a dose-dependent stimulation. ISO and VIP stimulation of cAMP were additive indicating action via independent receptors.