Catestatin attenuates the effects of intrathecal nicotine and isoproterenol

Gaede, Andrea H.; Lung, Mandy Siu Yu; Pilowsky, Paul M.

doi:10.1016/j.brainres.2009.09.088

Cited by 22 publications

(29 citation statements)

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“…General surgical methods were carried out as previously described (12,19). Briefly, anesthesia was induced in male Sprague-Dawley rats (n ϭ 22) with a bolus of urethane (ethyl carbamate, 10%, 1.3 g/kg ip in 0.9% saline wt/vol; Sigma-Aldrich).…”

Section: Surgical Proceduresmentioning

confidence: 99%

“…Cardiovascular reflexes were elicited at 10 min and 60 min post-PACAP-38 injection. The 15-min pretreatment period was chosen, because previously, intrathecal catestatin demonstrated its maximal effect on the nicotine response at 15 min (12).…”

Section: Experimental Protocolmentioning

confidence: 99%

“…Catestatin is contained within 88% of C1 RVLM neurons, and PACAP-38 is expressed in 85% of bulbospinal C1 RVLM neurons, indicating extensive colocalization of these neurotransmitters in this nucleus (9, 13). The separate effects of these peptides have been studied following injection into the intrathecal space and into the RVLM, (9,12,49,50), but the physiological significance of this extensive colocalization is unclear.Catestatin and PACAP are both vasodilator peptides in the periphery (11,54). Intrathecal PACAP increases splanchnic sympathetic nerve activity (sSNA) and heart rate (HR) but does not affect mean arterial blood pressure (MAP) (9).…”

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confidence: 99%

“…Catestatin is cardioprotective and blunts the sympathoexcitatory response to spinal stimulation in the pithed rat (23,35,43). In the spinal cord, catestatin stabilizes cardiovascular parameters by attenuating the responses to nicotine and isoproterenol (12). Catestatin may attenuate the ability of adenylate cyclase and phospholipase C to act intra-cellularly.…”

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Catestatin has an unexpected effect on the intrathecal actions of PACAP dramatically reducing blood pressure

Gaede

Inglott

Farnham

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Gaede AH, Inglott MA, Farnham MM, Pilowsky PM. Catestatin has an unexpected effect on the intrathecal actions of PACAP dramatically reducing blood pressure. Am J Physiol Regul Integr Comp Physiol 303: R719 -R726, 2012. First published August 8, 2012 doi:10.1152/ajpregu.00202.2012.-This study focuses on presympathetic neurons of the rostral ventrolateral medulla (RVLM) that regulate sympathetic vasomotor tone. Many neurotransmitters are colocalized in RVLM neurons and are released under specific conditions to modulate efferent homeostatic responses. Of particular interest here are two peptides colocalized in catecholaminergic RVLM neurons: catestatin and pituitary adenylate cyclase-activating polypeptide (PACAP). Chromogranin A-derived catestatin is a potent endogenous noncompetitive nicotinic and adrenoreceptor antagonist. Catestatin impairs adenylate cyclase and phospholipase C action: mechanisms engaged by PACAP. Although PACAP and catestatin are likely coreleased, the possible effects of this are unknown. We aimed to determine whether catestatin affects the normal sympathoexcitatory but isotensive responses to intrathecal PACAP. Urethane-anesthetized, vagotomized, ventilated Sprague-Dawley rats (n ϭ 22) were given an intrathecal injection of catestatin at different times prior to intrathecal administration of PACAP-38. Arterial pressure, splanchnic sympathetic nerve activity, heart rate, and reflex responses to baroreceptor and chemoreceptor activation were recorded. The key findings of this study are that pretreatment with catestatin time dependently enhances the PACAP-38 effect on mean arterial pressure and enhances sympathetic barosensitivity and chemosensitivity. The timescale of the effect of catestatin on the response to PACAP-38 strongly suggests that catestatin is either causing changes in gene expression to exert its effects, or modifying intracellular mechanisms normally engaged by PAC 1 receptors. The ability of catestatin pretreatment to enhance barosensitivity and chemosensitivity after PACAP-38 injection supports the hypothesis that catestatin manipulates the intracellular environment within sympathetic neurons in a way that increases responses to PACAP. chromogranin a; sympathetic; baroreflex; chemoreflex; epinephrine HYPERTENSION IS A MAJOR HUMAN health problem that is due, in large part, to increased sympathetic drive that emanates from the rostral ventrolateral medulla (RVLM) (42,44,45). Central neural mechanisms maintain arterial blood pressure by integrating information from reflexes and central behavioral and emotional states to alter efferent sympathetic and parasympathetic activity, according to need (18,44,45). The RVLM plays a critical role in this system as the final integrative pathway in the regulation of sympathetic tone and cardiovascular adaptive reflexes (e.g., the baroreceptor and chemoreceptor reflexes) (45). The RVLM contains a functionally heterogeneous cell population that includes barosensitive, presympathetic (C1) neurons, which project to sympathetic preganglionic neu...

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Section: Surgical Proceduresmentioning

confidence: 99%

Section: Experimental Protocolmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Catestatin has an unexpected effect on the intrathecal actions of PACAP dramatically reducing blood pressure

Gaede

Inglott

Farnham

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Chromogranin A: a novel susceptibility gene for essential hypertension

Sahu

Sonawane

Mahapatra

2009

Cell. Mol. Life Sci.

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Chromogranin A (CHGA) is ubiquitously expressed in secretory cells of the endocrine, neuroendocrine, and neuronal tissues. Although this protein has long been known as a marker for neuroendocrine tumors, its role in cardiovascular disease states including essential hypertension (EH) has only recently been recognized. It acts as a prohormone giving rise to bioactive peptides such as vasostatin-I (human CHGA(1-76)) and catestatin (human CHGA(352-372)) that exhibit several cardiovascular regulatory functions. CHGA is over-expressed but catestatin is diminished in EH. Moreover, genetic variants in the promoter, catestatin, and 3'-untranslated regions of the human CHGA gene alter autonomic activity and blood pressure. Consistent with these findings, targeted ablation of this gene causes severe arterial hypertension and ventricular hypertrophy in mice. Transgenic expression of the human CHGA gene or exogenous administration of catestatin restores blood pressure in these mice. Thus, the accumulated evidence establishes CHGA as a novel susceptibility gene for EH.

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Chromogranin A and Derived Peptides in Health and Disease

et al. 2012

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Chromogranin A (CgA) is a member of the granins, a family of acidic proteins found in abundance in (neuro)endocrine cells (e.g. in chromaffin cells) and in some tumors. Like other granins, CgA has a granulogenic role in secretory granule biogenesis and is stored in these organelles. CgA is partially processed differentially in various cell types to yield biologically active peptides, such as vasostatin, pancreastatin, catestatin and serpinins. In this review we describe the roles of CgA and several of its derived peptides. CgA, which is elevated in the blood of cancer patients, inhibits angiogenesis and exerts protective effects on the endothelial barrier function in tumors, thus affecting response to chemotherapy. Recent studies indicate that the serpinins promote cell survival and myocardial contractility and relaxation. Other peptides such as pancreastatin was found to have significant effects on inhibition of glucose stimulated insulin secretion and glucose up-take, induction of glycogenolysis in hepatocytes and inhibition of lipogenesis. In contrast, catestatin has opposite effects to that of pancreastatin in glucose metabolism and lipogenesis. Catestatin appears to also play a significant role in cardiac function, blood pressure regulation, and mutations in the catestatin domain of the CgA gene are associated with hypertension in humans.

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Catestatin attenuates the effects of intrathecal nicotine and isoproterenol

Cited by 22 publications

References 32 publications

Catestatin has an unexpected effect on the intrathecal actions of PACAP dramatically reducing blood pressure

Catestatin has an unexpected effect on the intrathecal actions of PACAP dramatically reducing blood pressure

Chromogranin A: a novel susceptibility gene for essential hypertension

Chromogranin A and Derived Peptides in Health and Disease

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