Department of Neurosurgery, Chi-Mei Medical Center, Yong Kang City, Tainan County 73101, Taiwan, ROC.
Neurosci Lett. 2010 Jan 14;468(3):297-9. doi: 10.1016/j.neulet.2009.11.018. Epub 2009 Nov 12.
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.
胍丁胺通过激动肾上腺髓质中的咪唑啉 I2 受体（I2R）增加β-内啡肽的释放，从而降低链脲佐菌素（STZ）诱导的糖尿病大鼠（STZ 大鼠）的血糖。然而，胍丁胺引起血糖降低作用的 I2R 亚型仍不清楚。在本研究中，胍丁胺处理增加了β-内啡肽的分泌，这种作用被 I2R 拮抗剂（BU224）阻断。我们进一步使用阿米洛利（一种已确立的 I2A 受体阻断剂）来鉴定肾上腺中的 I2R 亚型。结果表明，0.1μM 阿米洛利阻断了胍丁胺诱导的肾上腺β-内啡肽释放，表明 I2A 受体介导了这一作用。进一步证实，阿米洛利阻断了胍丁胺诱导的 STZ 大鼠血糖降低和血浆β-内啡肽增加。然而，阿米洛利未能在足以阻断β-内啡肽分泌的剂量下修饰胍丁胺（I2B 受体激动剂）的作用。综上所述，胍丁胺通过激活咪唑啉 I2R 增加 STZ 大鼠血浆β-内啡肽的作用主要是通过位于肾上腺的 I2A 亚型诱导的。因此，肾上腺中的咪唑啉 I2A 受体可能被用作诱导阿片肽分泌的新靶标。
