Uchida Sae, Hotta Harumi
Department of the Autonomic Nervous System, Tokyo Metropolitan Institute of Gerontology, Japan.
Biol Pharm Bull. 2009 Mar;32(3):341-4. doi: 10.1248/bpb.32.341.
Nicotinic acetylcholine receptors in the brain play a crucial role in the vasodilation in the cerebral cortex induced by basal forebrain cholinergic activation. Nicotinic receptors can be up-regulated or down-regulated in various conditions, e.g., up-regulation (increase in number) is found in smokers and in rodents exposed to chronic nicotine, while down-regulation (decrease in number) is found in elderly humans and in aged rats. We found in anesthetized rats that the increase in cortical cerebral blood flow induced by bolus intravenous nicotine injection was due to a vasodilation mediated by nitric oxide following activation of nicotinic receptors, probably of alpha4beta2-like subtype, both in the basal forebrain nuclei (Meynert nucleus) and in the cortex. This vasodilative response was reduced by long-term nicotine treatment and also in aged rats. Our results show that functional changes in nicotinic receptors are not always in the same direction as the changes in number; they highlight the importance of investigating not only the changes in receptor numbers but also those in their functional activity.
大脑中的烟碱型乙酰胆碱受体在基底前脑胆碱能激活诱导的大脑皮质血管舒张中起关键作用。烟碱型受体在各种情况下可上调或下调，例如，在吸烟者和暴露于慢性尼古丁的啮齿动物中发现上调（数量增加），而在老年人和老年大鼠中发现下调（数量减少）。我们在麻醉大鼠中发现，静脉推注尼古丁注射诱导的皮质脑血流量增加是由于烟碱型受体激活后一氧化氮介导的血管舒张，可能是α4β2样亚型，在基底前脑核（迈内特核）和皮质中均如此。长期尼古丁治疗以及老年大鼠中这种血管舒张反应均降低。我们的结果表明，烟碱型受体的功能变化并不总是与数量变化方向相同；它们强调了不仅要研究受体数量变化，还要研究其功能活性变化的重要性。
