Australian School of Advanced Medicine, Dow-Corning Bldg, Level 1, 3 Innovation Rd, Macquarie University, 2109, NSW, Australia.
Brain Res. 2009 Dec 11;1305:86-95. doi: 10.1016/j.brainres.2009.09.088. Epub 2009 Sep 26.
Catestatin (Cts; human chromogranin A(352-372)) is a neuropeptide derived from chromogranin A (ChgA). In the periphery it is released from the terminals of preganglionic neurons. In the adrenal medulla it inhibits catecholamine release by non-competitively antagonizing nicotinic cholinergic receptors. ChgA is present in the central nervous system, but the extent to which it is present within bulbospinal sympathoexcitatory neurons is unknown. We investigated the distribution of ChgA in the brainstem and its relationship to sympathoexcitatory neurons by combining immunofluorescence and in situ hybridization. A possible role for Cts in modulating the effect of other neurotransmitter systems in the spinal cord was examined by intrathecal injection of Cts, in conjunction with nicotine (1 microg-100 microg) and isoproterenol (0.12 microg-2.5 microg), in the anesthetized rat. Cts attenuated the hypotensive effect of isoproterenol on mean arterial pressure (maximum dose, 2.5 microg isoproterenol; -27 mmHg pre-Cts to -18 mmHg post-Cts), splanchnic sympathetic nerve activity (at 2.5 microg isoproterenol; 10.5% pre-Cts to 2.4% post-Cts), HR (at 2.5 microg isoproterenol; 1.1% pre-Cts to -1.6% post-Cts), and the dp/dt max of carotid pulse pressure (at 2.5 microg isoproterenol 17.3% pre-Cts to 9.3% post-Cts). Cts attenuated the hypertensive effect of nicotine on mean arterial pressure (at 10 microg nicotine, 19.3 mmHg pre-Cts to 6.8 mmHg post-Cts), splanchnic sympathetic nerve activity (at 10 microg nicotine, 10.7% pre-Cts to 4.5% post-Cts), and HR (at 10 microg nicotine, 4.1% pre-Cts to 2.0% post-Cts). The results indicate that Cts antagonizes both central nicotinic acetylcholine receptors and beta-adrenoceptors that are involved in cardiovascular regulation in vivo.
缩胆囊肽（Cts；人类嗜铬粒蛋白 A(352-372)）是一种源自嗜铬粒蛋白 A（ChgA）的神经肽。在周围神经系统中，它从节前神经元的末梢释放出来。在肾上腺髓质中，它通过非竞争性拮抗烟碱型乙酰胆碱受体来抑制儿茶酚胺的释放。ChgA 存在于中枢神经系统中，但它在球旁交感兴奋性神经元中的存在程度尚不清楚。我们通过免疫荧光和原位杂交相结合的方法研究了脑干中 ChgA 的分布及其与交感兴奋性神经元的关系。通过鞘内注射 Cts，并结合麻醉大鼠中的尼古丁（1μg-100μg）和异丙肾上腺素（0.12μg-2.5μg），研究了 Cts 在调节脊髓中其他神经递质系统的作用中的可能作用。Cts 减弱了异丙肾上腺素对平均动脉压（最大剂量 2.5μg 异丙肾上腺素；-27mmHg 预 Cts 至-18mmHg 后 Cts）、内脏交感神经活动（2.5μg 异丙肾上腺素；10.5%预 Cts 至 2.4%后 Cts）、心率（2.5μg 异丙肾上腺素；1.1%预 Cts 至-1.6%后 Cts）和颈动脉脉搏压 dp/dt max（2.5μg 异丙肾上腺素 17.3%预 Cts 至 9.3%后 Cts）的降压作用。Cts 减弱了尼古丁对平均动脉压（10μg 尼古丁时，19.3mmHg 预 Cts 至 6.8mmHg 后 Cts）、内脏交感神经活动（10μg 尼古丁时，10.7%预 Cts 至 4.5%后 Cts）和心率（10μg 尼古丁时，4.1%预 Cts 至 2.0%后 Cts）的升压作用。结果表明，Cts 拮抗体内心血管调节中涉及的中枢烟碱型乙酰胆碱受体和β-肾上腺素受体。
