The catecholamine release-inhibitory peptide catestatin (chromogranin A344-364) modulates myocardial function in fish

Abstract

ISO-and endothelin-1-induced positive inotropism and coronary constriction . Thus, besides its antihypertensive properties, CST is now emerging as a novel cardiac modulator, which would protect the heart against excessive systemic and/or intra-cardiac excitatory stimuli (e.g. catecholamines and endothelin-1). Accepted 4 August 2010 SUMMARY Catestatin (CST), the 21-amino acid, cationic and hydrophobic peptide proteolytically derived from the ubiquitous chromogranin A (CgA), is an endogenous inhibitor of catecholamine release, a potent vasodilator in vivo and an anti-hypertensive agent in mammals, including humans. Recently, we discovered that CST also functions as an important negative modulator of heart performance in frog and rat. To gain an evolutionary perspective on CST cardiotropism in fish, we analysed the influence of bovine CST (CgA 344-364 ) on the eel heart, as well as the eventual species-specific mechanisms of its myocardial action. Experiments were carried out on fresh-water eels (Anguilla anguilla L.) using an electrically paced isolated working heart preparation.

Phosphodiesterase type-2 and NO-dependentS-nitrosylation mediate the cardioinhibition of the antihypertensive catestatin

“…␤ 1 -AR, coupled to G s proteins, is responsible for positive inotropism and lusitropism, while ␤ 2 -AR, mainly coupled to G i/o proteins, is responsible for the opposite effects on contractility and relaxation (82). The heart of mammalian (23,24,69,2) and nonmammalian (33,49) vertebrates also expresses G i/o -protein-coupled ␤ 3 -AR, which induces negative inotropism and lusitropism (2,23). Activated by physio-pathological nor- adrenaline concentrations, ␤ 3 -ARs counteract the effects induced by catecholamine hyperstimulation (22).…”

“…We have recently shown that, in addition to its vasodilatory and antihypertensive influence, CST exerts inhibitory modulation on the mechanical performance of both basal and adrenergically stimulated cardiac preparations from eel (33), frog (49), and rat (2). Our ex vivo studies in the Langendorff-perfused rat heart revealed that CST dose dependently decreased left ventricular pressure (LVP), rate pressure product, and both positive and negative LVdP/dt.…”

Catestatin (Chromogranin A352–372) and Novel Effects on Mobilization of Fat from Adipose Tissue through Regulation of Adrenergic and Leptin Signaling

“…Initially identified as a physiological brake in catecholamine secretion (7), CST has been established as a pleiotropic hormone having effects on promoting angiogenesis (10), lowering of blood pressure (8,11,12), and cardiac contractility (13)(14)(15), as well as enhancing baroreflex sensitivity (16,17) and heart rate variability (18).…”

Hemodynamic Effects of Local Anesthesia and its Possible Correlation with Chromogranin A

“…[30] Catestatin is the first known endogenous compound able to inhibit in vitro catecholamine release from both chromaffin cells and noradrenergic neurons by acting as a non-competitive nicotinic cholinergic antagonist. [31] Angelone et al, (2008) [32] hypothesized that circulating levels of catestatin decreased in the plasma of patients with essential hypertension. Genetic ablation of the chromogranin A (Chga) gene in mice increases blood pressure and pretreatment of Chga-null mice with Cts prevents blood pressure elevation indicating a direct role of Cts in preventing hypertension.…”