Gandhi V C, Ross D H
Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284-7764.
Neurochem Res. 1987 Sep;12(9):801-7. doi: 10.1007/BF00971519.
The effects of alpha 1 and alpha 2-adrenergic receptor ligands on Ca2+/Mg2+-ATPase have been studied using synaptosomal plasma membranes isolated from rat brain cortex. Both phenylephrine and clonidine inhibited Ca2+/Mg2+-ATPase, in a concentration-dependent fashion. IC50 values for half-maximal inhibition for phenylephrine and clonidine were 29 microM and 18 microM, respectively. The inhibitory effect of phenylephrine was reversed by the alpha antagonist prazosin while yohimbine and rauwolscine reversed the inhibition of enzyme activity by clonidine. The two antagonist subtypes were effective only against the respective agonist subtypes, demonstrating distinct subtype preferences. Analysis of the kinetics of enzyme inhibition indicate both agonists to be noncompetitive. Some evidence suggests that yohimbine may exhibit mixed agonist/antagonist properties which depend on [Ca2+]. The present study provides biochemical evidence to support auto receptor alpha-adrenergic receptor regulation of neurotransmitter release.
利用从大鼠大脑皮层分离出的突触体细胞膜，研究了α1和α2肾上腺素能受体配体对Ca2+/Mg2+-ATP酶的影响。去氧肾上腺素和可乐定均以浓度依赖的方式抑制Ca2+/Mg2+-ATP酶。去氧肾上腺素和可乐定半数最大抑制浓度（IC50）分别为29微摩尔和18微摩尔。α拮抗剂哌唑嗪可逆转去氧肾上腺素的抑制作用，而育亨宾和萝芙素可逆转可乐定对酶活性的抑制作用。这两种拮抗剂亚型仅对各自的激动剂亚型有效，显示出明显的亚型偏好。酶抑制动力学分析表明，两种激动剂均为非竞争性的。一些证据表明，育亨宾可能表现出取决于[Ca2+]的混合激动剂/拮抗剂特性。本研究提供了生化证据，以支持神经递质释放的自身受体α-肾上腺素能受体调节。
