Schwartz D D, Eikenburg D C
Department of Pharmacology, College of Pharmacy, University of Houston, Texas.
J Pharmacol Exp Ther. 1989 Apr;249(1):177-83.
The effects of acute in vitro epinephrine treatment (40 nM, 1 hr) on stimulus-induced neurotransmitter overflow from the isolated perfused kidney were examined. This treatment resulted in the release of both norepinephrine and epinephrine upon nerve stimulation but no increase in fractional stimulus-induced overflow. Experiments utilizing beta and/or alpha adrenoceptor blockade revealed that beta adrenoreceptor blockade alone had no effect on overflow but that a dose-dependent decrease in stimulus-induced overflow was produced by beta adrenoceptor blockade after alpha adrenoceptor blockade. Thus, under normal conditions the facilitatory influence of epinephrine via prejunctional beta adrenoceptors is masked by the prejunctional alpha adrenoceptor negative feedback loop. The effects of extraneuronal presentation of isoproterenol, salbutamol and epinephrine on stimulus-induced neurotransmitter overflow also were examined. In the absence of alpha adrenoceptor blockade, only epinephrine failed to enhance neurotransmitter overflow. After competitive alpha adrenoceptor blockade, all three agents produced significant increases in stimulus-induced neurotransmitter overflow from the rat kidney, although alpha adrenoceptor stimulation appeared to limit this effect at high agonist concentrations. We conclude that the dominance of prejunctional alpha adrenoceptors in the rat kidney results in the inability of epinephrine to produce beta adrenoceptor-mediated facilitation of neurotransmitter overflow even when it is incorporated into renal neurotransmitter stores and coreleased with endogenous norepinephrine upon nerve stimulation.
研究了急性体外肾上腺素处理（40 nM，1小时）对离体灌注肾刺激诱导的神经递质溢出的影响。这种处理导致神经刺激时去甲肾上腺素和肾上腺素均释放，但刺激诱导的溢出分数无增加。利用β和/或α肾上腺素能受体阻断的实验表明，单独的β肾上腺素能受体阻断对溢出无影响，但在α肾上腺素能受体阻断后，β肾上腺素能受体阻断会导致刺激诱导的溢出呈剂量依赖性降低。因此，在正常情况下，肾上腺素通过突触前β肾上腺素能受体的促进作用被突触前α肾上腺素能受体负反馈环所掩盖。还研究了异丙肾上腺素、沙丁胺醇和肾上腺素的非神经元呈现对刺激诱导的神经递质溢出的影响。在没有α肾上腺素能受体阻断的情况下，只有肾上腺素未能增强神经递质溢出。竞争性α肾上腺素能受体阻断后，所有三种药物均使大鼠肾刺激诱导的神经递质溢出显著增加，尽管在高激动剂浓度下，α肾上腺素能受体刺激似乎会限制这种作用。我们得出结论，大鼠肾中突触前α肾上腺素能受体的主导地位导致即使肾上腺素被纳入肾神经递质储存并在神经刺激时与内源性去甲肾上腺素共同释放，它也无法产生β肾上腺素能受体介导的神经递质溢出促进作用。
