THE IMIDAZOLINE I-1 RECEPTOR AGONIST, MOXONIDINE, INHIBITS INSULIN-SECRETION FROM ISOLATED RAT ISLETS OF LANGERHANS

In order to study the pharmacology of the putative imidazoline recepto r involved in stimulation of insulin secretion, the potent and selecti ve imidazoline I-1 receptor agonist, moxonidine, was employed. Surpris ingly, this agent caused a rapid and complete inhibition of glucose-in duced insulin secretion in isolated rat islets of Langerhans. This res ponse was reversible upon removal of the compound but was only partial ly attenuated under conditions of complete alpha(2) blockade, suggesti ng that it did not derive entirely from the weak alpha(2)-adrenoceptor agonist activity of moxonidine. Furthermore, the response could not b e attributed to activation of imidazoline I-1 receptors since it was n ot reproduced by a second potent imidazoline I-1 receptor agonist, cim etidine, and could not be alleviated by the imidazoline I-1 receptor a ntagonist efaroxan. The results confirm that the imidazoline receptor involved in control of insulin secretion differs from the I-1 subclass and suggest that moxonidine inhibits insulin secretion by a mechanism unrelated to imidazoline I-1 receptor agonism.