Zahniser N R, Weiner G R, Worth T, Philpott K, Yasuda R P, Jonsson G, Dunwiddie T V
Pharmacol Biochem Behav. 1986 May;24(5):1397-402. doi: 10.1016/0091-3057(86)90201-7.
Following profound (greater than 90%) depletions of norepinephrine (NE) by the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4), the numbers of beta-adrenergic receptors were significantly increased (20-25%) in rat hippocampal and somatosensory cortical membranes; however, the numbers of alpha 1-adrenergic receptors and the affinities of both types of receptors were unaffected. This selective up-regulation of beta-adrenergic receptors was evident 1 week after DSP4 administration and was maintained for at least 2 more weeks. In electrophysiological experiments in the hippocampal slice preparation, responses to threshold as well as maximal concentrations of isoproterenol were enhanced 150% and 33%, respectively, in the DSP4-lesioned animals. The results demonstrate that nearly complete depletion of brain NE produced by administration of DSP4, like that produced by 6-hydroxydopamine, results in increased numbers of beta- but not alpha-adrenergic receptors, and suggest that the density of the former are regulated by afferent noradrenergic fibers. Furthermore, the functional significance of the increased number of hippocampal beta-adrenergic receptors is directly manifested in a greater electrophysiological responsiveness to an exogenously administered beta-adrenergic receptor agonist.
在用去甲肾上腺素能神经毒素N-(2-氯乙基)-N-乙基-2-溴苄胺（DSP4）使去甲肾上腺素（NE）深度耗竭（超过90%）后，大鼠海马和体感皮层膜中β-肾上腺素能受体的数量显著增加（20%-25%）；然而，α1-肾上腺素能受体的数量以及两种受体的亲和力均未受影响。这种β-肾上腺素能受体的选择性上调在给予DSP4后1周就很明显，并持续至少另外2周。在海马脑片制备的电生理实验中，在DSP4损伤的动物中，对阈浓度以及最大浓度异丙肾上腺素的反应分别增强了150%和33%。结果表明，给予DSP4导致的脑NE几乎完全耗竭，与6-羟基多巴胺导致的情况一样，会使β-而非α-肾上腺素能受体数量增加，并表明前者的密度受传入去甲肾上腺素能纤维的调节。此外，海马β-肾上腺素能受体数量增加的功能意义直接表现为对外源性给予的β-肾上腺素能受体激动剂具有更大的电生理反应性。
