Catestatin attenuates the effects of intrathecal nicotine and isoproterenol

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 noncompetitively 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 mu g-100 mu g)and isoproterenol (0.12 mu g-2.5 mu g), in the anesthetized rat. Cts attenuated the hypotensive effect of isoproterenol on mean arterial pressure (maximum dose, 2.5 mu g isoproterenol; -27 mmHg pre-Cts to -18 mmHg post-Cts), splanchnic sympathetic nerve activity (at 2.5 mu g isoproterenol; 10.5% pre-Cts to 2.4% post-Cts), HR (at 2.5 mu g isoproterenol; 1.1% pre-Cts to - 1.6% post-Cts), and the dp/dt max of carotid pulse pressure (at 2.5 mu g isoproterenol 17.3% pre-Cts to 9.3% post-Cts). Cts attenuated the hypertensive effect of nicotine on mean arterial pressure (at 10 mu g nicotine, 19.3 mmHg pre-Cts to 6.8 mmHg post-Cts), splanchnic sympathetic nerve activity (at 10 mu g nicotine, 10.7% pre-Cts to 4.5% post-Cts), and HR (at 10 mu g 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. Crown Copyright (C) 2009 Published by Elsevier B.V. All rights reserved.