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 beta-adrenoceptor in the intermediate lobe (IL) of the hypophysis of the rat is characterized on the basis of the following: 1) the ability of beta-adrenergic agonists to increase adenylate cyclase activity in homogenates of the IL, and 2) the ability of drugs active upon the beta-adrenoceptor to compete with [125I]hydroxybenzylpindolol, a radiolabeled beta-adrenergic antagonist, for high affinity (Kd = 232 pM) binding sites. The values of the affinity of the beta-adrenoceptor for drugs obtained in either assay system are in good agreement. The relative potency among agonists, L-isoproterenol greater than L-epinephrine greater than L-norepinephrine, suggests that the receptor is of the beta-2 subcategory. cAMP, derivatives of cAMP, and a phosphodiesterase inhibitor, theophylline, mimic the ability of l-isoproterenol to enhance the release of alpha MSH from dispersed cells of the rat IL. The present results are in accord with the possibility that occupancy by agonists of the beta-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 alpha MSH. Pharmacological data suggest that stimulation of a dopamine receptor in the IL diminishes the response of the beta-adrenoceptor to agonists.

Vasopressin Is not Involved in the Catecholamine-Induced Release of ACTH, α-MSH and β-Endorphin from the Rat Pituitary Gland

“…Results of studies with rats bearing hypothalamic lesions support the view that the P-adrenoceptor-mediated effect of catecholamines on ACTH and corticosterone (B) secretion require an intact hypothalamo-hypophysial connection [24], whereas the ef fect on a-MSH and P-endorphin from the melanotrophs is due to a direct action of catecholamines with P-adrenoceptor sites present on the melanotroph cells [2,20].…”

“…This is in disagreement with conclusions of Knepelet al [8], that may be based on a misinterpretation of their results since the secretion of a-MSH and other pep tides from the intermediate lobe can be inhibited by dexamethasone in doses as low as 250 pg/kg s.c. for at least 2 h [Berkenbosch et al, in prep.]. The effect of catecholamines on a-MSHi and P-ENDi secretion is most likely due to a di rect interaction of the catecholamines with P-adrenoceptor sites that are known to be present on the intermediate lobe cells [2,20], In conclusion, our data strongly support the view that vasopressin does not mediate the release of ACTH, p-endorphin and a-MSH following p-adrenoceptor stimulation.…”

The Pituitary Intermediate Lobe of the Hydrated and Dehydrated Gerbil

“…Although corticotrophin-releasing hormone, the main stimulatory factor of the corticotrophic cells, has some effect on melanotrophic cells [Meunier and Labrie, 1982], the regulation of the secretory activity of the melanotrophic cells is quite different from that of the corticotrophic cells. Melanotrophic cells are under tonic inhibitory control by the dopaminergic innervation mediated by D2 receptors which are negatively coupled to adenylate cyclase [Munemara et al, 1980]. Humoral regulation of the melanotrophic cells by circulating catecholamines is mediated by ß 2 -adrenergic receptors [Cote et al, 1980].…”

“…Melanotrophic cells are under tonic inhibitory control by the dopaminergic innervation mediated by D2 receptors which are negatively coupled to adenylate cyclase [Munemara et al, 1980]. Humoral regulation of the melanotrophic cells by circulating catecholamines is mediated by ß 2 -adrenergic receptors [Cote et al, 1980].…”

Stress-Induced Secretion of Pro-Opiomelanocortin-Derived Peptides in Rats: Relative Importance of the Anterior and Intermediate Pituitary Lobes

“…Accordingly, almost all circulating ACTH originates from the AL and almost all circulating a-MSH originates from the IL, whereas p-END originates from both the AL and IL [ 1,2], Secretion of POMC-derived peptides from the AL and IL is differentially regulated. Corticotropic cells are sub ject to humoral regulation and are primarily stimulated by the hypothalamic factors corticotropin-releasing hor mone (CRH) and arginine-vasopressin (AVP) and inhib ited by glucocorticoids [3,4], POMC secretion from the melanotropes is primarily controlled by neural regulation via stimulatory P-adrenergic input and inhibitory dopa minergic and y-aminobutyric acid (GABA)-ergic input [5][6][7][8]. Circulating catecholamines may also participate in regulation of the melanotropes.…”