Evidence for Y1 and Y2 subtypes of neuropeptide Y receptors linked to opposing postjunctional effects observed in rat cardiac myocytes.
The aim of this study was to confirm the existence of and identify the receptor subtypes for neuropeptide Y that are present post-junctionally in myocardium. The effects of the selective agonists, [Leu31, Pro34] neuropeptide Y (neuropeptide Y Y1 receptors), neuropeptide Y-(13-36) and peptide YY-(3-36) (neuropeptide Y Y2 receptors), and neuropeptide Y and the related peptide YY, which have differential action at neuropeptide Y Y3 receptors, on amplitudes of contraction of adult rat ventricular cardiomyocytes were studied. Also, the effect of the neuropeptide Y Y1-selective antagonist, bis(31/31')[[Cys31, Trp32, Nva34] neuropeptide Y-(31-36)] on neuropeptide Y-mediated changes in myocyte contraction was investigated. Neuropeptide Y, peptide YY, neuropeptide Y-(13-36) and peptide YY-(3-36) attenuated the isoprenaline (10(-7) M)-stimulated contractile response, and the EC50 values were 9.0 x 10(-9), 4.3 x 10(-10), 3.1 x 10(-11) and 8.5 x 10(-11) M, respectively. [Leu31, Pro34] neuropeptide Y increased the contractile response of cardiomyocytes, and the EC50 values were 8.1 x 10(-9) and 1.5 x 10(-9) M, in the absence and presence of isoprenaline, respectively. Since [Leu31, Pro34] neuropeptide Y caused a positive effect on ventricular myocyte contraction and neuropeptide Y-(13-36) and peptide YY (3-36) produced the most potent negative effects, it is proposed that both neuropeptide Y Y1 and neuropeptide Y Y2 receptors, linked respectively to the positive and negative responses, are expressed in cardiomyocytes. The finding of receptors with neuropeptide Y Y2 characteristics on cardiomyocytes represents a further example of a postjunctional location for this subtype. As there was no significant discrepancy between the potencies of peptide YY and neuropeptide Y to attenuate the contractile response, it appears that neuropeptide Y Y3-like receptors are not linked principally to contractile function in rat cardiomyocytes. Bis(31/31')[[Cys31, Trp32, Nva34] neuropeptide Y-(31-36)] antagonised the neuropeptide Y-mediated stimulation of contractile activity through neuropeptide Y Y1 receptors, but the compound also inhibited the attenuation of isoprenaline-stimulated contraction, apparently by acting as a partial agonist at the neuropeptide Y Y2 receptors.
McDermott
B J
BJ
Whitla Division of Medicine (Therapeutics and Pharmacology), The Queen's University of Belfast, Northern Ireland, UK.
Millar
B C
BC
Dolan
F M
FM
Bell
D
D
Balasubramaniam
A
A
D000818:Animals; D002478:Cells, Cultured; D006321:Heart / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000502:physiology*
D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y