Metabolic regulation by alpha 1- and alpha 2-adrenoceptors.
The role of alpha-adrenoceptors in the mediation of autonomic function, particularly in the control of the cardiovascular system, is widely known. However, alpha-adrenoceptors are also important in the regulation of a variety of metabolic processes that occur in the body either through direct action or by stimulation of the release of other mediators that control metabolic function. Thus, alpha 2-adrenoceptor activation by circulating or neuronally released catecholamines inhibits the release of insulin from pancreatic islet beta-cells and, by inhibiting this response, alpha 2-adrenoceptor antagonists have been shown to have an antihyperglycemic effect. The alpha-adrenoceptor-mediated regulation of the release of pituitary hormones is indirect, with alpha-adrenoceptors being located on peptidergic neurons in the hypothalamus that secrete releasing hormones into the hypophysial portal system to regulate the secretion of hormones from the anterior pituitary gland. Thus, the increase in cortisol secretion from the adrenal glands following a meal is produced, at least in part, by an alpha 1-adrenoceptor-mediated increase in vasopressin and CRF-41 secretion from neurons on the hypothalamus that stimulate the release of adrenocorticotrophic hormone secretion from the pituitary gland, which subsequently stimulates the synthesis and release of cortisol from the adrenal medulla. In addition to metabolic regulation by alpha 1- and alpha 2-adrenoceptors within the endocrine system, alpha-adrenoceptors are also a component of the system that regulates certain aspects of metabolism within autonomic effector cells, such as the control of smooth muscle cell division and growth during periods of continued alpha-adrenoceptor activation as a result of activation of second messenger systems.
Ruffolo
R R
RR
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406.
Nichols
A J
AJ
Hieble
J P
JP
D000818:Animals; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008066:Lipolysis; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000378:metabolism; D010907:Pituitary Hormones / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000145:classification / Q000502:physiology*; D015398:Signal Transduction
D007328:Insulin; D008074:Lipoproteins; D010907:Pituitary Hormones; D011942:Receptors, Adrenergic, alpha