Spessert R, Hill G, Vollrath L
Department of Anatomy, Johannes Gutenberg University, Mainz, Germany.
Brain Res. 1995 Oct 2;694(1-2):207-12. doi: 10.1016/0006-8993(95)00751-b.
There is ample evidence that beta-adrenergic stimulation of cyclic GMP formation is potentiated by alpha1-adrenergic mechanisms, the latter leading to elevation of intracellular Ca2+ concentration ([Ca2+]i) and protein kinase C (PKC) activation. Recent studies have shown that nitric oxide synthase (NOS) and nitric oxide (NO) are a component of the adrenoceptor-cyclic GMP signalling pathway. The aim of the present investigation was to study the roles of alpha1-adrenergic mechanisms, Ca2+ and PKC on NO-stimulated cyclic GMP formation. To this end suspension cultures of rat pinealocytes were treated with the NO donor sodium nitroprusside (SNP) in the presence of alpha1-adrenergic agonists, [Ca2+]i-elevating substances, PKC inhibitors, followed by measurement of cyclic GMP accumulation. It was found that alpha1-adrenergic stimulation did not affect NO-activated cyclic GMP synthesis. Therefore alpha1-mechanisms act prior to NO induction of cyclic GMP. Agents, which elevate [Ca2+]i depressed NO-induced cyclic GMP formation. Since literature data show that Ca2+ stimulates pineal NO formation it is apparent that Ca2+ has antagonistic effects in the pineal adrenoceptor-cyclic GMP signalling pathway. The inhibitory effect of Ca2+ was unchanged after inhibition of phosphodiesterases suggesting that it may interfere with cytosolic guanylyl cyclase activation. Inhibition of PKC, but not of other protein kinases, decreased NO-activated cyclic GMP formation. Therefore it appears that non-alpha1-adrenergic-regulated PKC possesses a regulatory rote in NO-induced cyclic GMP formation.
有充分证据表明，α1-肾上腺素能机制可增强β-肾上腺素能对环磷酸鸟苷（cGMP）形成的刺激作用，后者导致细胞内钙离子浓度（[Ca2+]i）升高和蛋白激酶C（PKC）激活。最近的研究表明，一氧化氮合酶（NOS）和一氧化氮（NO）是肾上腺素能受体 - 环磷酸鸟苷信号通路的组成部分。本研究的目的是探讨α1-肾上腺素能机制、钙离子和PKC在NO刺激的环磷酸鸟苷形成中的作用。为此，在α1-肾上腺素能激动剂、[Ca2+]i升高物质、PKC抑制剂存在的情况下，用NO供体硝普钠（SNP）处理大鼠松果体细胞悬液培养物，随后测量环磷酸鸟苷的积累。结果发现，α1-肾上腺素能刺激不影响NO激活的环磷酸鸟苷合成。因此，α1-机制在NO诱导环磷酸鸟苷之前起作用。升高[Ca2+]i的试剂可抑制NO诱导的环磷酸鸟苷形成。由于文献数据表明钙离子刺激松果体NO的形成，显然钙离子在松果体肾上腺素能受体 - 环磷酸鸟苷信号通路中具有拮抗作用。抑制磷酸二酯酶后，钙离子的抑制作用不变，这表明它可能干扰胞质鸟苷酸环化酶的激活。抑制PKC而非其他蛋白激酶，可降低NO激活的环磷酸鸟苷形成。因此，似乎非α1-肾上腺素能调节的PKC在NO诱导的环磷酸鸟苷形成中具有调节作用。
