Identification and Characterization of Non-Adrenergic Binding Sites in Insulin-Secreting Cells with the Imidazoline RX821002

Abstract

Recent studies have shown that certain compounds which possess an imidazoline moiety within their structure, are able to enhance the rate of insulin secretion, both in vivo and in vitro ¹. ⁸⁶Rb⁺ efflux experiments and electrophysiological studies^2,3 have provided evidence that this response is due to the reduction in potassium flux via ATP-regulated K⁺ channels across the islet B-cell plasma membrane, resulting in membrane depolarization. The nature of the binding site mediating the effects of imidazolines in islets is unclear but it is significant that a class of binding sites known as “imidazoline-preferring” receptors has recently been described in a wide variety of tissues⁴. However, the pharmacology of the defined I₁- and I₂-imidazoline sites does not correlate with the observed responses to imidazolines in islets, although I₂-receptors (also known as non-adrenoceptor idazoxan binding sites (NAIBS)) have been described in pancreatic islets⁵ and RINm5F insulinoma cells⁶. Moreover, we have shown that the secretory response induced by the imidazoline efaroxan shows stereoselectivity and is subject to down-regulation in the presence of agonist⁷. Thus, the possibilty remains the islet imidazoline receptor may represent a novel, third type of imidazoline binding site.