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| Barreto,F.; Rezende,D.C.; Scaramello,C.B.V.; Silva,C.L.M.; Cunha,V.M.N.; Caricati-Neto,A.; Jurkiewicz,A.; Noël,F.; Quintas,L.E.M.. |
| 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... |
| Tipo: Info:eu-repo/semantics/article |
Palavras-chave: Α1B-adrenoceptors; Ca2+-ATPases; Cardiac hypertrophy; Na+/K+-ATPase; Mitogen-activated protein kinases. |
| Ano: 2010 |
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2010000500012 |
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| Noël,F.; Nascimento-Viana,J.B.; Romeiro,L.A.S.; Silva,R.O.; Lemes,L.F.N.; Oliveira,A.S.; Giorno,T.B.S.; Fernandes,P.D.; Silva,C.L.M.. |
| This study aimed to estimate the absorption, distribution, metabolism and excretion (ADME) properties and safety of LDT5, a lead compound for oral treatment of benign prostatic hyperplasia that has previously been characterized as a multi-target antagonist of α1A-, α1D-adrenoceptors and 5-HT1A receptors. The preclinical characterization of this compound comprised the evaluation of its in vitro properties, including plasma, microsomal and hepatocytes stability, cytochrome P450 metabolism and inhibition, plasma protein binding, and permeability using MDCK-MDR1 cells. De-risking and preliminary safety pharmacology assays were performed through screening of 44 off-target receptors and in vivo tests in mice (rota-rod and single dose toxicity). LDT5 is stable in... |
| Tipo: Info:eu-repo/semantics/article |
Palavras-chave: Benign prostatic hyperplasia; ADME; Safety; Permeability; CYP; Preclinical development. |
| Ano: 2016 |
URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2016001200603 |
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