Increase of beta-endorphin secretion by agmatine is induced by activation of imidazoline I(2A) receptors in adrenal gland of rats.

Activation of imidazoline I(2) receptor (I(2)R) by agmatine in adrenal gland lowers plasma glucose through increment in beta-endorphin release to stimulate the opioid mu-receptor in streptozotocin-induced diabetic rats (STZ rats). However, the subtype of I(2)R for agmatine-induced blood glucose lowering effect remains obscure. In the present study, agmatine treatment increased beta-endorphin secretion and this effect was blocked by I(2)R antagonist (BU224) in the isolated adrenal medulla. We further used amiloride, an established blocker of I(2A)R, to identify the subtype of I(2)R in adrenal gland. Results showed that agmatine-induced beta-endorphin release from adrenal gland was blocked by 0.1muM amiloride indicating the mediation of I(2A)R. It was further confirmed that agmatine-induced plasma glucose decrement and plasma beta-endorphin increment in STZ rats were blocked by amiloride. However, amiloride failed to modify the action of guanidine, an agonist of I(2B)R, at the sufficient dose to block beta-endorphin secretion. Taken together, the increase of plasma beta-endorphin by agmatine in STZ rats through activation of imidazoline I(2)R was mainly induced by the I(2A) subtype located in adrenal gland. Thus, imidazoline I(2A) receptor in the adrenal gland might be applied as a new target for induction of opioid secretion.