The characteristics of beta-adrenergic binding sites on pancreatic islets of Langerhans.

The sympathetic nervous system is believed to play a part in the control of insulin release from the pancreatic islets of Langerhans. Stimulation of alpha-adrenoceptors is thought to inhibit the release of insulin whereas stimulation of beta-adrenoceptors enhances insulin release. The present experiments were conducted to establish the existence of beta-adrenergic receptors on guinea-pig and rat islet cells and to quantify them using the selective beta-adrenergic ligands [3H]dihydroalprenolol (DHA) and [125I]cyanoiodopindolol (CYP). Guinea-pig islets had 62 fmol beta-adrenoceptors/mg protein using [3H]DHA, corresponding to 43,700 binding sites/cell and 25 fmol beta-adrenoceptors/mg protein using [125I]CYP, corresponding to 17,400 sites/cell. Rat islet cells were found to have 4.6 fmol beta-adrenoceptors/mg protein using [125I]CYP, corresponding to 7200 sites/cell. Adenylate cyclase activation exhibited a positive dose-response relationship when exposed to the beta-adrenoceptor agonist isoprenaline, with a maximum response (190 +/- 21% above basal) at 10 mumol isoprenaline/l. This response was abolished with 1 mumol/l of the beta-adrenergic antagonist l-alprenolol. Insulin secretion in the presence of 10 mmol glucose/l, but in the absence of the alpha-adrenoceptor blocker phentolamine, was not affected by 10 mumol isoprenaline/l. However, perifusion experiments showed that secretion of insulin from isolated rat islets in the presence of 10 mmol glucose/l was significantly increased (332%) by 10 mumol isoprenaline/l in the presence of 10 mumol phentolamine/l. These results suggest that binding of selective radiolabelled ligands occurs to beta-adrenergic receptors on the B cell surface of the islets of Langerhans, and that these receptors are functionally coupled to insulin secretion through modulation of adenylate cyclase activity.