Atrial natriuretic peptide mRNA regulation by p38-MAPK in the perfused amphibian heart.

Atrial natriuretic peptide (ANP) is a cardiac hormone involved in the regulation of fluid balance and blood pressure homeostasis. Using conventional reverse transcription and polymerase chain reaction and amplification, preproANP transcript from Rana ridibunda heart ventricle was cloned and characterized. Sequence analysis of the complete cDNA revealed an open reading frame for a 146residue peptide, carrying a 17-residue ring at the Cterminus, characteristic of the natriuretic peptide family. Perfusion of Rana ridibunda myocardium under diverse stimuli such as mechanical, hyperosmotic or oxidative stress induced a rapid increase in the transcripts, which is accompanied by a significant increase in phosphorylated p38-MAPK levels. Furthermore, 1 μM SB203580, the selective p38-MAPK inhibitor, was found to abolish this increase suggesting the involvement of the p38-MAPK signalling pathway in the regulation of ANP mRNA expression. Introduction Natriuretic peptides (NPs), acting mainly via particulate guanylate cyclase receptors, are polypeptide hormones with important cardioinhibitory effects [1]. They are secreted by the myocardium and are involved in sodium secretion and blood pressure control in a wide range of organisms [2-4]. The family of natriuretic peptides consists of three structurally similar peptides: the atrial natriuretic peptide (ANP), the brain natriuretic peptide (BNP) and the C-type natriuretic peptide (CNP) [4]. They all have a characteristic 17 amino-acid residue ring structure formed by an intra-molecular disulfide bridge between two cysteine residues [5-6]. The sequencing of the NPs has revealed an elevated structural homology between different species, confirming their high conservation [4]. Cardiac natriuretic peptides are secreted upon relevant stimuli such as stretch of the atrial myocytes. However, the ventricular myocytes become progressively the major site of peptide secretion during cellular stresses, which are related to hypertrophy [7-8]. Among the various signal transduction pathways activated by diverse stressful stimuli the mitogen activated protein kinases (MAPKs) are included. Three subfamilies of the MAPKs have been clearly identified and D ow nl oa de d by : 54 .1 91 .4 0. 80 4 /2 5/ 20 17 1 0: 58 :1 1 P M