title: Lack of evidence for regulation of cardiac P-type ATPases and MAP kinases in transgenic mice with cardiac-specific overexpression of constitutively active alpha(1B)-adrenoceptors.
abstract: The regulatory function of alpha(1B)-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 Ca(2+)-ATPases) and growth (ERK1/2, JNK1/2 and p38) in mice with cardiac-selective overexpression of constitutively active mutant alpha1B-adrenoceptor (CAMalpha(1B)-AR), which present a mild cardiac hypertrophy phenotype. Immunoblot assays showed that myocardial plasma membrane Ca(2+)-ATPase (PMCA) expression was increased by 30% in CAMalpha(1B)-AR mice (N = 6, P < 0.05), although there was no change in sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA2) expression. Moreover, total Ca(2+)-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 alpha(1) and alpha(2) subunit isoforms was changed in CAMalpha(1B)-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 alpha(1B)-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.
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, RJ, Brasil.
authors.forename: F
authors.initials: F
authors.lastname: Barreto
authors.forename: D C
authors.initials: DC
authors.lastname: Rezende
authors.forename: C B V
authors.initials: CB
authors.lastname: Scaramello
authors.forename: C L M
authors.initials: CL
authors.lastname: Silva
authors.forename: V M N
authors.initials: VM
authors.lastname: Cunha
authors.forename: A
authors.initials: A
authors.lastname: Caricati-Neto
authors.forename: A
authors.initials: A
authors.lastname: Jurkiewicz
authors.forename: F
authors.initials: F
authors.lastname: Noël
authors.forename: L E M
authors.initials: LE
authors.lastname: Quintas
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018340:Receptors, Adrenergic, alpha-1; D020928:Mitogen-Activated Protein Kinases; D000251:Adenosine Triphosphatases