Neurotransmitter receptors mediate cyclic GMP formation by involvement of arachidonic acid and lipoxygenase.
Neurotransmitter receptors mediate cyclic GMP formation by involvement of arachidonic acid and lipoxygenase.
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DOI：
10.1073/pnas.81.12.3905
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发表时间：
1984-06
影响因子：
11.1
通讯作者：
R. Snider;Michael McKinney;Carlos Forray;Elliott Richelson
中科院分区：
文献类型：
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作者：
R. Snider;Michael McKinney;Carlos Forray;Elliott Richelson
有证据表明，在培养的神经细胞中，受体介导的环状GMP的形成是通过细胞外钙离子的内流和胞内游离钙离子浓度的增加来实现的。虽然周期性的GMP反应完全依赖于钙离子的存在，但激动剂刺激后细胞内游离钙离子并没有增加。相反，我们发现毒鼠碱或组胺H1受体的刺激通过奎尼卡林敏感的机制，可能是磷脂酶A2，引起花生四烯酸的释放。通过脂氧合酶途径抑制花生四烯酸的释放或代谢，可以阻止受体介导的环状GMP的形成。我们假设，介导环状GMP合成的神经递质受体通过释放花生四烯酸发挥作用，然后花生四烯酸的氧化代谢产物刺激可溶性鸟苷环化酶。
Evidence is presented that has led us to abandon the hypothesis that receptor-mediated cyclic GMP formation in cultured nerve cells occurs via the influx of extracellular calcium ions and an increase in the cytosolic free calcium ion concentration. While the cyclic GMP response is absolutely dependent on the presence of Ca2+, there is no increase in free intracellular Ca2+ subsequent to agonist stimulation. Instead, we have found that muscarinic or histamine H1 receptor stimulation elicits the release of arachidonic acid through a quinacrine-sensitive mechanism, possibly phospholipase A2. Inhibition of the release or metabolism of arachidonate by the lipoxygenase pathway prevents receptor-mediated cyclic GMP formation. We hypothesize that neurotransmitter receptors that mediate cyclic GMP synthesis function by releasing arachidonic acid and that an oxidative metabolite of arachidonic acid then stimulates soluble guanylate cyclase.