Intracellular signalling involved in the regulation of atrial natriuretic factor secretion

Abstract

Atrial natriuretic factor (ANF) is a hormone that helps maintain fluid homeostasis and has many other physiological roles. Understanding of its regulation may have immense impacts in the treatment and understanding of cardiac diseases. Despite the recent and continuing unravelling of signalling cascades, the intracellular signalling governing ANF secretion from atrial cardiocytes remains mostly unknown. Following recent evidence of the involvement of G proteins in modulating ANF secretion, the role of Gq effector phospholipase C (PLC) and its proximal effectors was investigated in spontaneously beating rat atria. Phospholipase C and protein kinase C inhibitors dramatically increased basal secretion of ANF. Furthermore, although stretch is a potent stimulus for secretion, these inhibitor-mediated increases fell to baseline levels when the stretch of the atria was subsequently introduced. Inositol trisphosphate receptor inhibition did not appear to affect basal secretion but dose-dependently blocked stretch secretion coupling. These results reveal interesting novel phenomena and demonstrate key participation of the PLC cascade in the regulation of ANF secretion.