Increase of β-endorphin secretion by agmatine is induced by activation of imidazoline I_2A receptors in adrenal gland of rats

Activation of imidazoline I₂ receptor (I₂R) by agmatine in adrenal gland lowers plasma glucose through increment in β-endorphin release to stimulate the opioid μ-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 β-endorphin secretion and this effect was blocked by I₂R antagonist (BU224) in the isolated adrenal medulla. We further used amiloride, an established blocker of I_2AR, to identify the subtype of I₂R in adrenal gland. Results showed that agmatine-induced β-endorphin release from adrenal gland was blocked by 0.1 μM amiloride indicating the mediation of I_2AR. It was further confirmed that agmatine-induced plasma glucose decrement and plasma β-endorphin increment in STZ rats were blocked by amiloride. However, amiloride failed to modify the action of guanidine, an agonist of I_2BR, at the sufficient dose to block β-endorphin secretion. Taken together, the increase of plasma β-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.