Lack of Inotropic Effects of Neuropeptide Y in Human Myocardium

Mc, Machado; Sc, Wirth; Hr, Zerkowski; ́as, M. Kap; Hj, Motulsky

doi:10.1097/00005344-198912000-00019

Cited by 30 publications

(11 citation statements)

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“…Y1 receptor expression in the myocardium of the adult atrial appendage also coincides with the distribution of NPY-immunoreactive nerves (25), although studies in vitro have indicated that NPY has no direct effect on human myocardial contractility (26,27).…”

Section: Methodsmentioning

confidence: 88%

Expression of the human neuropeptide tyrosine Y1 receptor.

Wharton

Gordon

Byrne

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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Neuropeptide tyrosine (NPY) is the predominant peptide in the innervation of many human tissues and is considered to play a role in the regulation of blood flow, gastrointestinal secretion and motility, and renal function. Three NPY receptors have been identified (Y1, Y2, and Y3) and the cDNAs encoding the human Y1 and bovine Y3 receptors have recently been cloned. We have demonstrated the expression of the Yl receptor subtype in several fetal and adult human tissues, including the colon, kidney, adrenal gland, heart, and placenta. A single transcript was identified (%2.2 kb) and localized in tissue sections by in situ hybridization. In the colon the receptor is expressed in the mucosa and basal glands, as well as the myenteric and submucous plexuses. Y1 receptor mRNA was detected in renal collecting ducts, loop of Henle, and juxtaglomerular apparatus and in the syncytiotrophoblast layer of placental villi. Fetal aorta and adult intramyocardial, colonic, and renal blood vessels also exhibited receptor expression, localized to the intima as well as the media. The distribution of Yl receptor expression correlates with that of NPY-immunoreactive nerves and the apparent actions ofNPY in the intestine, kidney, and heart. Although the placenta is devoid of nerves, an NPY-like transcript was detected in the villous trophoblast layer. The results indicate a tissue-specific regulation of NPY Y1 receptor expression.Neuropeptide tyrosine (NPY) is an amidated 36-amino acid peptide found in both the central and peripheral nervous systems and is a member of a family of regulatory peptides which also includes peptide tyrosine tyrosine (PYY) (1). NPY is localized together with norepinephrine in sympathetic nerves and is widely distributed in the innervation of the human cardiovascular system, kidney, and gastrointestinal tract, as well as other organs (2, 3). In addition to its neural localization, NPY-like immunoreactivity has also been demonstrated in adrenal medullary cells (4) and the villous trophoblast layer in the placenta (5). PYY immunoreactivity exhibits a distinct distribution pattern and is localized to endocrine cells in the human colon (6). These peptides have both direct and indirect effects on blood flow, gastrointestinal secretion and motility (3), and renal function (7) (3,5,(9)(10)(11). Furthermore, the relevance of these studies to humans is uncertain due to species variation in both receptor distribution and peptide metabolism and the apparent difficulty in demonstrating specific NPY binding sites in human tissues (12). Following the recent cloning of human and bovine NPY receptor cDNA sequences (13,14), it is now possible to circumvent many of these problems by using specific molecular probes and in situ hybridization techniques to determine the localization of mRNA encoding NPY receptor subtypes. When expressed in vitro, the human receptor displays a rank order of agonist potency [NPY = PYY > [Leu31,Pro34]NPY >> NPY-(13-36)] characteristic of the Y1 receptor subtype (13). We have used radiolabeled...

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Section: Methodsmentioning

confidence: 88%

Expression of the human neuropeptide tyrosine Y1 receptor.

Wharton

Gordon

Byrne

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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“…It has been shown to inhibit release of catecholamines and regulate the vasoconstrictor action of norepinephrine. Neuropeptide Y has also been shown to produce vasoconstriction of coronary vessels in many species, including human (Michel et al, 1989). Neuropeptide Y is first seen late in development in the region of the sinus and atrioventricular nodes and in the intrinsic cardiac ganglia.…”

Section: Hmentioning

confidence: 99%

Autonomic innervation of the developing heart: Origins and function

2008

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Maintenance of homeostatic circulation in mammals and birds is reliant upon autonomic innervation of the heart. Neural branches of mixed cellular origin and function innervate the heart at the arterial and venous poles as it matures, eventually coupling autonomic output to the cardiac components, including the conduction system. The development of neural identity is controlled by specific networks of genes and growth factors, whereas functional properties are governed by the use of different neurotransmitters. In this review, we summarize briefly the anatomic arrangement of the vertebrate autonomic nervous system and describe, in detail, the innervation of the heart. We discuss the timing of cardiac innervation in the chick and mouse, emphasizing the relationship of the cardiac neural networks to the anatomical structures within the heart. We also discuss the variable contribution of the neural crest to vagal cardiac nerves, and summarize the main neurotransmitters secreted by the developing sympathetic and parasympathetic autonomic divisions. We provide an overview of the main growth factor and gene families involved in neural development, discussing how these factors may impact upon the development of cardiac abnormalities in congenital syndromes associated with autonomic dysfunction.

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“…Thus, NPY has been shown to exert positive, negative, or no effects on cardiac muscle strips (Malmström and Lundberg 1997). Inotropy was not affected by NPY in human atrial strips (Franco-Cereceda et al 1987;Michel et al 1989). Negative inotropic effects of NPY were demonstrated in adult rat cardiomyocytes and the opposite was shown in those of adult guinea pig (Millar et al 1991).…”

Section: Introductionmentioning

confidence: 96%

Neuropeptide Y induced increase of cytosolic and nuclear Ca²⁺in heart and vascular smooth muscle cells

Jacques¹,

Sader²,

El-Bizri³

et al. 2000

Can. J. Physiol. Pharmacol.

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It was reported that neuropeptide Y (NPY) affects cardiac and vascular smooth muscle (VSM) function probably by increasing intracellular Ca2+. In this study, using fura-2 microfluorometry and fluo-3 confocal microscopy techniques for intracellular Ca2+ measurement, we attempted to verify whether the action of NPY receptor's stimulation in heart and VSM cells modulates intracellular Ca2+ and whether this effect is mediated via the Y1 receptor type. Using spontaneously contracting single ventricular heart cells of 10-day-old embryonic chicks and the fluo-3 confocal microscopy Ca2+ measurement technique to localize cytosolic ([Ca]c) and nuclear ([Ca]n) free Ca2+ level and distribution, 10-10 M of human (h) NPY significantly (P < 0.05) increased the frequency of cytosolic and nuclear Ca2+ transients during spontaneous contraction. Increasing the concentration of hNPY (10(-9) M) did not further increase the frequency of Ca2+ transients. The L-type Ca2+ channel blocker, nifedipine (10(-5) M), significantly (P < 0.001) blocked the spontaneous rise of intracellular Ca2+ in the absence and presence of hNPY (10(-10) and 10(-9) M). However, the selective Y1 receptor antagonist, BIBP3226 (10(-6) M), significantly decreased the hNPY-induced (10(-10) and 10(-9) M) increase in the frequency of Ca2+ transients back to near the control level (P < 0.05). In resting nonworking heart and human aortic VSM cells, hNPY induced a dose-dependent sustained increase of basal resting intracellular Ca2+ with an EC50 near 10(-9) M. This sustained increase was cytosolic and nuclear and was completely blocked by the Ca2+ chelator EGTA, and was significantly decreased by the Y1 receptor antagonist BIBP3226 in both heart (P < 0.05) and VSM (P < 0.01) cells. These results strongly suggest that NPY stimulates the resting basal steady-state Ca2+ influx through the sarcolemma and induces sustained increases of cytosolic and nuclear calcium, in good part, via the activation of the sarcolemma membrane Y1 receptor type in both resting heart and VSM cells. In addition, NPY also increased the frequency of Ca2+ transients during spontaneous contraction of heart cells mainly via the activation of the Y1 receptor type, which may explain in part the active cardiovascular action of this peptide.

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Lack of Inotropic Effects of Neuropeptide Y in Human Myocardium

Cited by 30 publications

References 0 publications

Expression of the human neuropeptide tyrosine Y1 receptor.

Expression of the human neuropeptide tyrosine Y1 receptor.

Autonomic innervation of the developing heart: Origins and function

Neuropeptide Y induced increase of cytosolic and nuclear Ca²⁺in heart and vascular smooth muscle cells

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Lack of Inotropic Effects of Neuropeptide Y in Human Myocardium

Cited by 30 publications

References 0 publications

Expression of the human neuropeptide tyrosine Y1 receptor.

Expression of the human neuropeptide tyrosine Y1 receptor.

Autonomic innervation of the developing heart: Origins and function

Neuropeptide Y induced increase of cytosolic and nuclear Ca2+in heart and vascular smooth muscle cells

Contact Info

Product

Resources

About

Neuropeptide Y induced increase of cytosolic and nuclear Ca²⁺in heart and vascular smooth muscle cells