Biochemical Identification of the β-Adrenoceptor and Evidence for the Involvement of an Adenosine 3′,5′-Monophosphate System in the β-Adrenergically Induced Release of a-Melanocyte-Stimulating Hormone in the Intermediate Lobe of the Rat Pituitary Gland

Abstract

The β-adrenoceptor in the intermediate lobe (IL) of the hypophysis of the rat is characterized on the basis of the following: 1) the ability of β-adrenergic agonists to increase adenylate cyclase activity in homogenates of the IL, and 2) the ability of drugs active upon the β-adrenoceptor to compete with [^l2I]hydroxybenzylpindolol, a radiolabeled β-adrenergic antagonist, for high affinity (K_d = 232 pin) binding sites. The values of the affinity of the β-adrenoceptor for drugs obtained in either assay system are in good agreement. The relative potency among agonists,lisoproterenol > lepinephrine > lnorepinephrine, suggests that the receptor is of the β-2 subcategory. cAMP, derivatives of cAMP, and a phosphodiesterase inhibitor, theophylline, mimic the ability of lisoproterenol to enhance the release of aMSH from dispersed cells of the rat IL. The present results are in accord with the possibility that occupancy by agonists of the β-adrenoceptor of the IL enhances adenylate cyclase activity, resulting in an accumulation of cAMP which initiates the intracellular events that are ultimately expressed as an enhanced release of αMSH. Pharmacological data suggest that stimulation of a dopamine receptor in the IL diminishes the response of the β-adrenoceptor to agonists.