Saphier D, Welch J E
Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport.
J Pharmacol Exp Ther. 1994 Sep;270(3):905-17.
The mechanism by which the 5-hydroxytryptamine1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) increases adrenocortical secretion was examined using treatments designed to alter the hypothalamo-pituitary-adrenocortical axis and the autonomic nervous system. Adrenocortical responses to peripherally administered 8-OH-DPAT were preserved in animals with radiofrequency lesions of the hypothalamic paraventricular nucleus or with posterior hypothalamic deafferentations. However, adrenocortical responses to 8-OH-DPAT were abolished in hypophysectomized animals, although both acute and chronic treatment with dexamethasone were without effect. The influence of catecholamines in the central and sympathetic nervous systems was investigated using treatments designed to alter central and peripheral catecholaminergic systems. Adrenocortical responses after intracerebroventricular administration of high doses of 8-OH-DPAT were attenuated by i.v. and intra-adrenal treatment with 6-hydroxydopamine (6-OHDA), by adrenal medullectomy, by splanchnicectomy and by combined 6-OHDA-sympathectomy/medullectomy. Responses to i.p. 8-OH-DPAT were only partially attenuated by medullectomy and by 6-OHDA-sympathectomy/medullectomy. The ganglionic blocking agent, chlorisondamine also blocked the adrenocortical response after intracerebroventricular, but not i.p., administration of 8-OH-DPAT. These effects did not appear to be due to surgical damage to the adrenal cortex because the operated animals showed normal adrenocortical responses to challenge with adrenocorticotropic hormone. The data obtained indicate that adrenocortical secretion in response to i.p. and intracerebroventricular administration of the 5-hydroxytryptamine1A receptor agonist 8-OH-DPAT largely involves a sympathomedullary activation, but that additional peripheral mechanisms are also involved after i.p. administration.
使用旨在改变下丘脑 - 垂体 - 肾上腺皮质轴和自主神经系统的处理方法，研究了5 - 羟色胺1A激动剂8 - 羟基 - 2 - （二正丙基氨基）四氢萘（8 - OH - DPAT）增加肾上腺皮质分泌的机制。在患有下丘脑室旁核射频损伤或下丘脑后部去传入神经的动物中，对外周给予的8 - OH - DPAT的肾上腺皮质反应得以保留。然而，在垂体切除的动物中，对8 - OH - DPAT的肾上腺皮质反应被消除，尽管地塞米松的急性和慢性治疗均无效果。使用旨在改变中枢和外周儿茶酚胺能系统的处理方法，研究了儿茶酚胺在中枢和交感神经系统中的作用。脑室内给予高剂量8 - OH - DPAT后的肾上腺皮质反应，通过静脉内和肾上腺内给予6 - 羟基多巴胺（6 - OHDA）、肾上腺髓质切除术、内脏神经切除术以及联合6 - OHDA - 交感神经切除术/髓质切除术而减弱。对腹腔注射8 - OH - DPAT的反应仅被髓质切除术和6 - OHDA - 交感神经切除术/髓质切除术部分减弱。神经节阻断剂氯异吲哚铵也阻断了脑室内（而非腹腔内）给予8 - OH - DPAT后的肾上腺皮质反应。这些效应似乎并非由于对肾上腺皮质的手术损伤，因为手术动物对促肾上腺皮质激素刺激显示出正常的肾上腺皮质反应。所获得的数据表明，腹腔内和脑室内给予5 - 羟色胺1A受体激动剂8 - OH - DPAT后，肾上腺皮质分泌在很大程度上涉及交感 - 髓质激活，但腹腔内给药后也涉及其他外周机制。
