RESUMO
We have developed a specific radioimmunoassay (RIA) for iso-rANP(1-45)/rBNP(51-95) using antiserum produced against a peptide comprise of the first 20 amino acid sequence of this cardiac hormone. Using this RIA, we found that atria contained the highest amount of iso-rANP(1-45) (567.37 pmol/g) which is about 140-fold higher than ventricles (4.32 pmol/g). With the exception of the lung and kidney, all other tissues had negligible amounts. The plasma level was 1.4 fmol/ml and the only molecular form found was the 45 amino acid form. HPLC analysis of extracts of isolated, purified atrial granules revealed that, like atrial natriuretic peptide (ANP), iso-rANP/rBNP is also stored in these granules. However, while ANP is stored predominantly as pro-ANP(1-126) and cleaved during or after release, iso-ANP/BNP is stored as the 45 amino acid form and may be processed prior to storage in the granules.
Assuntos
Fator Natriurético Atrial/análise , Fator Natriurético Atrial/sangue , Grânulos Citoplasmáticos/química , Miocárdio/química , Proteínas do Tecido Nervoso/análise , Proteínas do Tecido Nervoso/sangue , Sequência de Aminoácidos , Animais , Reações Antígeno-Anticorpo , Fator Natriurético Atrial/imunologia , Átrios do Coração/química , Dados de Sequência Molecular , Peptídeo Natriurético Encefálico , Proteínas do Tecido Nervoso/imunologia , Coelhos , Radioimunoensaio , Ratos , Ratos Sprague-DawleyRESUMO
We have reported that a second rat atrial natriuretic peptide, iso-rANP (1-45), as well as the putative ANP homologue, iso-rANP (17-45), elicited circulatory and renal responses in the rat similar to those found after administration of ANP. Iso-rANP also interacted with ANP to potentiate the observed biological activity in the rat. In the present studies in awake dogs, intravenous infusion of low doses (6.3-50 pmol.kg-1.min-1) of iso-rANP(1-45) and iso-rANP(17-45) increased plasma immunoreactive ANP and suppressed plasma renin activity (PRA) and aldosterone. Iso-rANP, like ring-deleted analogues of ANP, may have displaced ANP from ANP clearance receptors to increase plasma ANP concentration, since factors influencing myocardial ANP release were not changed. The effect of iso-rANP (1-45) and (17-45) in lowering PRA and plasma aldosterone may therefore have been indirect, via ANP stimulation of active guanylate cyclase-linked ANP receptors. However, an additional direct effect of iso-rANP on an active receptor cannot be excluded.
