EVIDENCE FOR Y-1 AND Y-2 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-junctional ly in myocardium. The effects of the selective agonists, [Leu(31), Pro (34)] neuropeptide Y (neuropeptide Y Y-1 receptors), neuropeptide Y-(1 3-36) and peptide YY-(3-36) (neuropeptide Y Y-2 receptors), and neurop eptide Y and the related peptide YY, which have differential action at neuropeptide Y Y-3 receptors, on amplitudes of contraction of adult r at ventricular cardiomyocytes were studied. Also, the effect of the ne uropeptide Y Y-1-selective antagonist, bis(31/31'){[Cys(31), Trp(32), Nva(34)] neuropeptide Y-(31-36)} on neuropeptide Y-mediated changes in myocyte contraction was investigated. Neuropeptide Y, peptide YY, neu ropeptide 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, respect ively. [Leu(31), Pro(34)] neuropeptide Y increased the contractile res ponse 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 [Leu(31), Pro(34)] 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 t hat both neuropeptide Y Y-1 and neuropeptide Y Y-2 receptors. linked r espectively to the positive and negative responses, are expressed in c ardiomyocytes. The finding of receptors with neuropeptide Y Y-2 charac teristics on cardiomyocytes represents a further example of a postjunc tional location for this subtype. As there was no significant discrepa ncy between the potencies of peptide YY and neuropeptide Y to attenuat e the contractile response, it appears that neuropeptide Y Y-3-like re ceptors are not linked principally to contractile function in rat card iomyocytes. Bis(31/31'){[Cys(31), Trp (32), Nva(34)] neuropeptide Y-(3 1-36)} antagonised the neuropeptide Y-mediated stimulation of contract ile activity through neuropeptide Y Y-1 receptors, but the compound al so inhibited the attenuation of isoprenaline-stimulated contraction, a pparently by acting as a partial agonist at the neuropeptide Y Y-2 rec eptors. (C) 1997 Elsevier Science B.V.