Increase of β-endorphin secretion by agmatine is induced by activation of imidazoline I2A receptors in adrenal gland of rats

Activation of imidazoline I-2 receptor (I2R) 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 I2R 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 I2R antagonist (BU224) in the isolated adrenal medulla. We further used amiloride, an established blocker Of I2AR, to identify the subtype Of I2R in adrenal gland. Results showed that agmatine-induced beta-endorphin release from adrenal gland was blocked by 0.1 mu M amiloride indicating the mediation Of I2AR. 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 I2BR, 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 I2R 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. (C) 2009 Elsevier Ireland Ltd. All rights reserved.