Displacement of Alpha- and Beta-Radioligands by Specific Adrenergic Agonists in Rat Pancreatic Islets

Abstract

Secretion of insulin is increased by β-adrenergic agonists and inhibited by α-adrenergic agonists. However, administration of epinephrine, which acts on both types of receptors, inhibits insulin secretion. A preliminary study using [³H]-dihydroergocryptine and [³H]-dihydroalprenolol as the respective α- and β-receptor binding ligands, surprisingly revealed a preponderance of β-binding sites in normal rat pancreatic islets. The present study, using displacement by epinephrine, norepinephrine, isoproterenol and clonidine validated the use of these radioligands as appropriate for specific receptor binding in pancreatic islet cells. The islets were found to have 55 fmol/mg protein of α-adrenergic receptor sites and 170 fmol/mg protein of β-receptor sites. The affinity of both α- and β-receptors for epinephrine was similar, as judged by the displacement of either radioligand, thus ruling out a preferential affinity of α-receptor binding as an explanation for the α-inhibition of insulin secretion. The data on radioligand displacement by clonidine indicate that the α-receptor is of the α_2-type.

Studies on the mechanism of inhibition of glucose-stimulated insulin secretion by noradrenaline in rat islets of Langerhans

“…3). This result is consistent with the inhibitory effect of noradrenaline in mouse islets (Ismail et al, 1983) and confirms that, although apparently few in number (Cherksey et al, 1983) islet-cell ax-receptors have the potential to modulate islet function in response to local changes in noradrenaline concentration. In this context, it is noteworthy that local sympathetic tone has been directly implicated in the homoeostatic control of insulin secretion in the rat (Curry, 1983).…”

Pharmacological Agents That Directly Modulate Insulin Secretion

“…There is physiologic and pharmacologic evidence for the presence of inhibitory and stimulatory adrenoreceptors on the ␤-cell. The inhibitory ␣-adrenoreceptor has been characterized as being of the ␣ 2 -subtype (Cherksey et al, 1983) and the stimulatory ␤-adrenoreceptor as the ␤ 2 -subtype (Fyles et al, 1986). The ␣ 2 -subtype is coupled to G i /G o , and the ␤ 2 is coupled to the G s protein.…”

Characterization of α2-adrenoceptors in a plasma membrane enriched fraction from the insulin-secreting cell line RINm5F

“…The epinephrine-induced inhibition of insulin release has been shown to be counteracted by specific a2-adrenergic antagonists sugges¬ ting the presence of this adrenergic receptor sub¬ type on the ß-cell surface (4). A few binding studies have been performed on isolated rat islet cell prep¬ arations demonstrating the presence of a2-adrenoceptors (5)(6)(7)(8). The cell heterogeneity of islets (only 60-70% of an islet are insulin-secreting cells) and the limited amount of purified pancreatic ß-cell material available made the use of established cell lines to study cellular events involved in insulin se¬ cretion very attractive.…”