Lack of evidence for regulation of cardiac P-type ATPases and MAP kinases in transgenic mice with cardiac-specific overexpression of constitutively active α1B-adrenoceptors

Brazilian Journal of Medical and Biological Research

F. Barreto²  D.c. Rezende²  C.b.v. Scaramello¹  C.l.m. Silva²  V.m.n. Cunha²  A. Caricati-neto¹  A. Jurkiewicz¹  F. Noël²  L.e.m. Quintas² 

[1] ,Universidade Federal do Rio de Janeiro Instituto de Ciências Biomédicas Programa de FarmacologiaRio de Janeiro RJ ,Brasil

关键词: α1B-adrenoceptors;    Ca2+-ATPases;    Cardiac hypertrophy;    Na+/K+-ATPase;    Mitogen-activated protein kinases;   

DOI  :  10.1590/S0100-879X2010007500028

来源: SciELO

【 摘 要 】

The regulatory function of α1B-adrenoceptors in mammalian heart homeostasis is controversial. The objective of the present study was to characterize the expression/activity of key proteins implicated in cardiac calcium handling (Na+/K+-ATPase and Ca2+-ATPases) and growth (ERK1/2, JNK1/2 and p38) in mice with cardiac-selective overexpression of constitutively active mutant α1B-adrenoceptor (CAMα1B-AR), which present a mild cardiac hypertrophy phenotype. Immunoblot assays showed that myocardial plasma membrane Ca2+-ATPase (PMCA) expression was increased by 30% in CAMα1B-AR mice (N = 6, P < 0.05), although there was no change in sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2) expression. Moreover, total Ca2+-ATPase activity was not modified, but a significant increase in the activity of the thapsigargin-resistant (PMCA) to thapsigargin-sensitive (SERCA) ratio was detected. Neither Na+/K+-ATPase activity nor the expression of α1 and α2 subunit isoforms was changed in CAMα1B-AR mouse hearts. Moreover, immunoblot assays did not provide evidence for an enhanced activation of the three mitogen-activated protein kinases studied in this stage of hypertrophy. Therefore, these findings indicate that chronic cardiac α1B-AR activation in vivo led to mild hypertrophy devoid of significant signs of adaptive modifications concerning primary intracellular calcium control and growth-related proteins, suggesting a minor pathophysiological role of this adrenergic receptor in mouse heart at this stage of development.

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