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大脑皮质毒蕈碱胆碱能受体和N-甲基-D-天冬氨酸受体介导导水管周围灰质化学刺激引起的皮质血流增加。

Cerebral cortical muscarinic cholinergic and N-methyl-D-aspartate receptors mediate increase in cortical blood flow elicited by chemical stimulation of periaqueductal gray matter.

作者信息

Nakai M, Maeda M

机构信息

National Cardiovascular Center Research Institute, 565-8565, Osaka, Japan.

出版信息

Neuroscience. 2000;98(3):449-57. doi: 10.1016/s0306-4522(00)00105-6.

DOI:10.1016/s0306-4522(00)00105-6
PMID:10869839
Abstract

The periaqueductal gray matter is implicated in the central processing of defensive reactions. We found previously that, when stimulated by N-methyl-D-aspartate, the caudal third of its lateral subdivision elicited an increase in blood flow over widespread cerebral neocortical areas and that a major proportion of the flow increase was inhibited by topical cortical application of scopolamine, an antagonist of muscarinic receptors. The present study was undertaken to elucidate the roles of cortical nicotinic and excitatory amino acid receptors in the mediation of the flow increase in 66 anaesthetized, cervically cordotomized, artificially ventilated rats with open cranial windows. We found that the flow increase (laser-Doppler flowmetry) was resistant to antagonists of non-N-methyl-D-aspartate receptors and of nicotinic receptors. The response was, however, attenuated to a substantial extent by topical and intravenous N-methyl-D-aspartate receptor antagonists, MK-801 and topical D(-)-2-amino-5-phosphonopentanoic acid. Combined topical application of the latter antagonist with scopolamine attenuated the flow increase to a further extent beyond that achieved with either of the antagonists alone. Topical applications of acetylcholine and N-methyl-D-aspartate individually increased the cortical blood flow. A modest synergism was observed between the actions of these two agonists.Overall, we suggest that in the face of stimuli which provoke defensive reactions, the periaqueductal gray matter may elicit an increase in cortical blood flow by utilizing the cortical acetylcholine-muscarinic receptor system and the cortical excitatory amino acid-N-methyl-D-aspartate receptor system. The vasomotor actions of these two transmitter-receptor systems may operate independently of each other as well as in harmony with each other.

摘要

导水管周围灰质与防御反应的中枢处理有关。我们先前发现,当受到N-甲基-D-天冬氨酸刺激时,其外侧亚区的尾侧三分之一会引起广泛大脑新皮质区域的血流增加,并且大部分血流增加可被局部应用毒蕈碱受体拮抗剂东莨菪碱所抑制。本研究旨在阐明皮质烟碱受体和兴奋性氨基酸受体在66只麻醉、颈髓横断、人工通气且开颅窗的大鼠中血流增加介导过程中的作用。我们发现血流增加(激光多普勒血流仪检测)对非N-甲基-D-天冬氨酸受体拮抗剂和烟碱受体拮抗剂有抗性。然而,局部和静脉注射N-甲基-D-天冬氨酸受体拮抗剂MK-801和局部应用D-(-)-2-氨基-5-膦酸戊酸可使反应在很大程度上减弱。后一种拮抗剂与东莨菪碱联合局部应用可使血流增加的减弱程度超过单独使用任何一种拮抗剂时所达到的程度。单独局部应用乙酰胆碱和N-甲基-D-天冬氨酸均可增加皮质血流。在这两种激动剂的作用之间观察到适度的协同作用。总体而言,我们认为面对引发防御反应的刺激时,导水管周围灰质可能通过利用皮质乙酰胆碱-毒蕈碱受体系统和皮质兴奋性氨基酸-N-甲基-D-天冬氨酸受体系统来引起皮质血流增加。这两个递质-受体系统的血管舒缩作用可能彼此独立发挥作用,也可能相互协调发挥作用。

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