Induction of hypertrophic responsiveness of cardiomyocytes to neuropeptide Y in response to pressure overload

被引:22
作者
Bell, D
Allen, AR
Kelso, EJ
Balasubramaniam, A
McDermott, BJ
机构
[1] Queens Univ Belfast, Sch Med, Ctr Cardiovasc & Genet Res, Dept Therapeut & Pharmacol, Belfast BT9 7BL, Antrim, North Ireland
[2] Univ Cincinnati, Med Ctr, Dept Surg, Div Gastrointestinal Hormones, Cincinnati, OH 45267 USA
关键词
D O I
10.1124/jpet.102.038448
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
To determine whether neuropeptide Y (NPY)-related mechanisms become activated with progression of cardiac hypertrophy in vivo, protein mass and de novo protein synthesis (incorporation of [C-14] Phe, 0.1 muCi ml(-1)) were assessed in cardiomyocytes, obtained from spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (8, 12, 16, 20, and 24 weeks of age), and cultured for 24 h. NPY (10(-8) M) increased protein mass of cardiomyocytes from 16-week-old SHRs by 9.2 +/- 2.1% (n = 8, P < 0.05). De novo protein synthesis was increased maximally in SHRs at 12, 16, and 20 weeks (P < 0.05, n = 8) in response to NPY by 12.6 +/- 2.1% (10(-6) M), 20.1 +/- 4.2% (10(-8) M), and 9.4 +/- 1.8% (10(-7) M), respectively. Peptide YY3-36, (PYY3-36), which displays selectivity for NPY Y-2 and NPY Y-5 receptors, and the NPY Y-5 selective agonist [D-Trp(34)]-NPY increased de novo protein synthesis maximally by 16.2 +/- 5.1% (10(-7) M; n = 4, P < 0.05) and 17.8 +/- 5.2% (10(-6) M; n = 7, P < 0.05), respectively, in SHRs at 16 weeks, whereas [Leu(31)Pro(34)]- NPY (less than or equal to10(-6) M), which displays some activity at NPY Y-1 and NPY Y-4 receptors, did not. The NPY Y-1-selective antagonist BVD-42 (2 x 10(-7) M) and the NPY Y-2-selective antagonist BIIE0246 (2 x 10(-7) M) did not attenuate responses to NPY (10(-7) M) and PPY3-36 (10(-7) M). These data indicate that hypertrophic responsiveness to NPY, mediated via NPY Y5 receptors, is induced transiently in SHR cardiomyocytes subsequent to onset of cardiomyocyte hypertrophy in response to pressure overload.
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页码:581 / 591
页数:11
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