Alterations in messenger rna encoding atrial natriuretic hormone receptor A and C subtypes during hepatic regeneration

Previously, we demonstrated that, 48 hours after partial hepatectomy, in the regenerating liver the number of both atrial natriuretic hormone (ANF) receptor subtypes, the guanylyl cyclase-linked and ANF-C receptors, is increased twofold. Subsequently, we demonstrated that activation of ANF-C receptors inhibits growth of hepatocytes. Therefore, studies were performed to determine whether, during hepatic regeneration, the increase in ANF receptor subtypes is accompanied by an increase in their respective transcripts. Our data demonstrate that in the normal and regenerating rat liver, the predominant guanylyl cyclase-linked ANF receptor is of the ANF-A subtype. Moreover, messenger RNA (mRNA) encoding the ANF-A and ANF-C receptors are transiently increased after surgery; the levels of mRNA encoding both receptor subtypes remain unchanged in livers of sham-operated animals. ANF-A receptor mRNA is maximally increased 12 hours after partial hepatectomy, whereas the maximal increase in ANF-C receptor mRNA is observed between 0.5 hour and 4 hours after hepatectomy. The increase in ANF-C receptor transcript is accompanied by increased expression of protein, 4 hours after hepatectomy. However, the ANF-C receptor protein is also elevated 48 hours after partial hepatectomy when ANF-C receptor mRNA levels are not different from controls. Likewise, although ANF-A receptors are increased when hepatic levels of mRNA encoding the protein are maximally elevated, the maximal increase in ANF-A receptor protein occurs at times when transcript levels are low and similar to those in sham-operated controls.(ABSTRACT TRUNCATED AT 250 WORDS)