Arakawa K, De Jong W, Mulder A H, Versteeg D H
Department of Pharmacology, Rudolf Magnus Institute, Medical Faculty, University of Utrecht, The Netherlands.
Eur J Pharmacol. 1991 Jan 10;192(2):311-6. doi: 10.1016/0014-2999(91)90057-w.
The electrically stimulated release of [3H]noradrenaline ([3H]NA) from slices of the nucleus tractus solitarii (NTS) from the rat in vitro was inhibited by the alpha 2-adrenoceptor agonist, clonidine, in a concentration-dependent manner and enhanced by the alpha 2-adrenoceptor antagonist, yohimbine. Phenylephrine, isoprenaline, carbachol, quinpirole and SKF 38393, all at 10(-6) M, did not affect the stimulus-evoked release of [3H]NA. The opioid peptides, alpha- and gamma-endorphin, did not have a significant effect on the stimulus-evoked release of [3H]NA; however, beta-endorphin reduced it in a concentration-dependent manner. [Leu5]Enkephalin also reduced [3H]NA release, but higher concentrations were necessary. The selective delta opioid receptor agonists, [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Ser2(O-tert-butyl),Leu5]enkephalyl-Thr6 (DSTBULET), as well as the selective kappa opioid receptor agonist, U-69593, were not effective. The selective mu opioid receptor agonist, [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAGO), concentration dependently reduced the stimulus-evoked release of [3H]NA to the same extent as beta-endorphin did. Naloxone, while having no effect on stimulus-evoked [3H]NA release, antagonized the effect of DAGO. These results corroborate that the release of NA from noradrenergic terminals in the NTS region of the medulla oblongata of the rat is modulated via alpha 2-adrenoceptors and suggest that the release of NA in the NTS in rats is also modulated via mu opioid receptors.
在体外实验中，大鼠孤束核（NTS）切片中，α2 -肾上腺素能受体激动剂可乐定以浓度依赖的方式抑制电刺激诱发的[3H]去甲肾上腺素（[3H]NA）释放，而α2 -肾上腺素能受体拮抗剂育亨宾则增强其释放。苯肾上腺素、异丙肾上腺素、卡巴胆碱、喹吡罗和SKF 38393（均为10(-6) M）均不影响刺激诱发的[3H]NA释放。阿片肽α -内啡肽和γ -内啡肽对刺激诱发的[3H]NA释放无显著影响；然而，β -内啡肽以浓度依赖的方式降低其释放。[亮氨酸5]脑啡肽也降低[3H]NA释放，但需要更高浓度。选择性δ阿片受体激动剂[D - Pen2，D - Pen5]脑啡肽（DPDPE）和[D - Ser2（O -叔丁基），亮氨酸5]脑啡肽 -苏氨酸6（DSTBULET）以及选择性κ阿片受体激动剂U - 69593均无效。选择性μ阿片受体激动剂[D - Ala2，NMePhe4，Gly - ol5]脑啡肽（DAGO）与β -内啡肽一样，以浓度依赖的方式降低刺激诱发的[3H]NA释放。纳洛酮虽然对刺激诱发的[3H]NA释放无影响，但可拮抗DAGO的作用。这些结果证实，大鼠延髓NTS区域去甲肾上腺素能终末的NA释放通过α2 -肾上腺素能受体进行调节，并提示大鼠NTS中NA的释放也通过μ阿片受体进行调节。
