J Korean Med Sci.  2008 Dec;23(6):1027-1032. 10.3346/jkms.2008.23.6.1027.

Different Regulation of Atrial ANP Release through Neuropeptide Y2 and Y4 Receptors

• Piao FL
• Yuan K
• Bai GY
• Han JH
• Park WH
• Kim SH

• KMID: 1107529
• DOI: http://doi.org/10.3346/jkms.2008.23.6.1027

Abstract

Neuropeptide Y (NPY) receptors are present in cardiac membranes. However, its physiological roles in the heart are not clear. The aim of this study was to define the direct effects of pancreatic polypeptide (PP) on atrial dynamics and atrial natriuretic peptide (ANP) release in perfused beating atria. Pancreatic polypeptides, a NPY Y4 receptor agonist, decreased atrial contractility but was not dose-dependent. The ANP release was stimulated by PP in a dose-dependent manner. GR 23118, a NPY Y4 receptor agonist, also increased the ANP release and the potency was greater than PP. In contrast, peptide YY (3-36) (PYY), an NPY Y2 receptor agonist, suppressed the release of ANP with positive inotropy. NPY, an agonist for Y1, 2, 5 receptor, did not cause any significant changes. The pretreatment of NPY (18-36), an antagonist for NPY Y3 receptor, markedly attenuated the stimulation of ANP release by PP but did not affect the suppression of ANP release by PYY. BIIE0246, an antagonist for NPY Y2 receptor, attenuated the suppression of ANP release by PYY. The responsiveness of atrial contractility to PP or PYY was not affected by either of the antagonists. These results suggest that NPY Y4 and Y2 receptor differently regulate the release of atrial ANP.

Keyword

Pancreatic Polypeptide; Peptide YY; Neuropeptide Y; Atrial Natriuretic Factor; Receptor; Contractility

MeSH Terms

Animals
Arginine/analogs & derivatives/pharmacology
Atrial Natriuretic Factor/*metabolism
Benzazepines/pharmacology
Gene Expression Regulation
Pancreatic Polypeptide/pharmacology
Peptide YY/pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Neuropeptide Y/agonists/antagonists & inhibitors/*metabolism

Figure

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  Fig. 1 (A) Effects of pancreatic polypeptide (10-8M, n=6; 10-7M, n=8; 3×10-7M, n=7) on pulse pressure, ECF translocation, ANP secretion, and ANP concentration in isolated perfused beating rat atria. Pancreatic polypeptide decreased atrial contractility without change in ECF translocation. The ANP secretion and concentration gradually increased in terms of time. (B) Relative percent changes in pulse pressure, ECF translocation, ANP secretion, and ANP concentration by pancreatic polypeptide. Values were expressed as percent changes of the five peak experimental values for exposure to pancreatic polypeptide, as compared to the mean of the five control values. Pancreatic polypeptide increased the ANP secretion in a dose-dependent manner. Arrow indicates the start time of peptide infusion. PP, pancreatic polypeptide; CONT, control group; ECF transloc, ECF translocation; ANP conc, ANP concentration. *p<0.05; †p<0.01 vs. corresponding dose.

• 

  Fig. 2 (A) Effects of pancreatic polypeptide (PP, 10-7M, n=8), GR 23118 (10-7M, n=6), neuropeptide Y (NPY, 10-7M, n=8), and peptide YY (3-36) (PYY, 10-7M, n=7) on pulse pressure, ECF translocation, ANP secretion, and ANP concentration in isolated perfused beating rat atria. GR 23118 decreased atrial contractility and ECF translocation, and increased the ANP secretion. In contrast, peptide YY (3-36) increased atrial contractility and ECF translocation. The ANP secretion and concentration gradually decreased in terms of time. Neuropeptide Y also decreased the ANP secretion without significant changes in atrial contractility and ECF translocation. (B) Comparison of relative percent changes in several parameters between GR 23118, neuropeptide, peptide YY (3-36) and pancreatic polypeptide. Values were expressed as percent changes of the three peak experimental values for exposure to neuropeptide family, as compared to mean of the five control values. There was a significant difference in changes in ANP secretion by GR 23118, neuropeptide Y, and peptide YY (3-36), as compared to pancreatic polypeptide. Legends are the same as in Fig. 1. *p<0.05; †p<0.01 vs. pancreatic polypeptide-exposed group.

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  Fig. 3 Comparison of relative percent changes in pulse pressure (A), ECF translocation (B), ANP secretion (C), and ANP concentration (D) by pancreatic polypeptide (PP, 10-7M, n=7) and peptide YY (3-36) (PYY, 10-7M, n=7) in the presence and absence of neuropeptide (18-36) (3×10-7M, n=7) and BIIE0246 (3×10-7M, n=7). Pancreatic polypeptide-stimulated ANP secretion was attenuated by neuropeptide (18-36) and peptide YY (3-36)-suppressed ANP secretion was attenuated by BIIE0246. Legends are the same as in Fig. 1. *p<0.05; †p<0.01 vs. the control group.

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