THROMBIN STIMULATES ATRIAL-NATRIURETIC-PEPTIDE SECRETION FROM RAT CARDIAC ATRIUM

Atrial natriuretic peptide (ANP) is a hormone secreted predominantly b y atrial myocytes. Although atrial distension is the primary stimulus of ANP secretion, several hormones have also been implicated in the re gulation ANP secretion. alpha-Thrombin, a serine protease participatin g in the blood coagulation system, has additional hormone-like effects in several cell types, apparently via interaction with specific cell surface receptors. Here we report that alpha-thrombin enhanced ANP sec retion From isolated rat atrium within 10 min, in a concentration-depe ndent manner. The protease also significantly increased ANP release fr om cultured atrial myocytes, in a concentration-dependent manner. The alpha-thrombin-induced release of ANP from cultured atrial myocytes wa s completely abolished by hirudin, a specific alpha-thrombin protease inhibitor. Furthermore, synthetic peptides, identical in their amino a cid sequence to the N-terminal segment of the proteolytically cleaved thrombin receptor, enhanced ANP release from adult rat cultured atrial myocytes. Our data suggest that thrombin may regulate ANP release fro m the cardiac atrium. This action involves activation of thrombin rece ptors in atrial myocytes.