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蓝斑或背侧去甲肾上腺素能束刺激对外侧膝状体神经元的激活:α1肾上腺素能受体拮抗剂哌唑嗪的选择性阻断作用

Activation of lateral geniculate neurons by locus coeruleus or dorsal noradrenergic bundle stimulation: selective blockade by the alpha 1-adrenoceptor antagonist prazosin.

作者信息

Rogawski M A, Aghajanian G K

出版信息

Brain Res. 1982 Oct 28;250(1):31-9. doi: 10.1016/0006-8993(82)90950-7.

Abstract

Presentation of a stimulus train to the locus coeruleus (LC) or dorsal noradrenergic bundle (DB) resulted in a facilitation of the spontaneous firing of single units in the dorsal lateral geniculate nucleus (LGNd) of the rat. These stimulation effects were blocked by the alpha 1-adrenoceptor antagonists WB-4101 and prazosin. Both drugs also blocked the activation of LGNd neurons by iontophoretic norepinephrine (NE). The cholinergic agonists acetylcholine (ACh) and carbachol (CCh) activated LGNd neurons in a similar fashion to NE, however, these responses were selectively blocked by the muscarinic antagonist scopolamine. The response to ACh was also sensitive to WB-4101 suggesting that the drug possesses some cholinergic blocking activity. In contrast to WB-4101, prazosin displayed a high degree of selectivity for noradrenergic but not cholinergic responses. On the basis of the observation that prazosin selectively antagonizes both the stimulation effects and iontophoretic NE (but not CCh), we conclude that activation of LGNd neurons by LC or DB stimulation is mediated predominantly via the release of NE from coeruleo-geniculate fibers, rather than the inadvertent activation of a cholinergic pathway. Moreover, inasmuch as the systemic administration of prazosin effectively blocks central noradrenergic neurotransmission at doses comparable to those used clinically, the possibility that prazosin exerts its antihypertensive action in part via a central mechanism requires further investigation.

摘要

向大鼠蓝斑(LC)或背侧去甲肾上腺素能束(DB)施加一串刺激会促进大鼠背外侧膝状核(LGNd)中单个神经元的自发放电。这些刺激效应被α1 - 肾上腺素能拮抗剂WB - 4101和哌唑嗪阻断。这两种药物也阻断了离子电渗法给予去甲肾上腺素(NE)对LGNd神经元的激活。胆碱能激动剂乙酰胆碱(ACh)和卡巴胆碱(CCh)以与NE相似的方式激活LGNd神经元,然而,这些反应被毒蕈碱拮抗剂东莨菪碱选择性阻断。对ACh的反应也对WB - 4101敏感,表明该药物具有一些胆碱能阻断活性。与WB - 4101不同,哌唑嗪对去甲肾上腺素能反应表现出高度选择性,而对胆碱能反应则不然。基于哌唑嗪选择性拮抗刺激效应和离子电渗法给予的NE(但不包括CCh)这一观察结果,我们得出结论,LC或DB刺激对LGNd神经元的激活主要是通过蓝斑 - 膝状体纤维释放NE介导的,而不是通过意外激活胆碱能通路。此外,由于临床使用剂量的哌唑嗪全身给药可有效阻断中枢去甲肾上腺素能神经传递,哌唑嗪部分通过中枢机制发挥其降压作用的可能性需要进一步研究。

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