Heterotrimeric G(i/o) proteins regulate stretch-stimulated ANF secretion in isolated rat atria.

Abstract

Atrial wall stretch plays an important role in regulating the secretion of ANF, a cardiac peptide hormone that regulates water and salt balance, as well as blood pressure. Yet the precise cellular mechanism that couples mechanical stretch to ANF secretion is unknown. In order to elucidate this mechanism, we investigated the role of heterotrimeric Gi/o proteins in mechanically-stimulated ANF secretion. G proteins act as molecular switches that have been implicated in the control of intracellular protein transport, and stretch-secretion coupling. We utilized a pharmalogical agent, pertussis toxin (PTX), to inhibit Gi/o proteins in male Sprague Dawley rats. The effect of stimulating Gi/o proteins was also investigated using Mastoparan-7 (MAS-7; 10-5 M). Infusion with MAS-7 for 30 minutes potently stimulated ANF secretion; a response attenuated by. Results suggest that Gi/o proteins couple atrial muscle stretch to ANF secretion in an acute setting, and that there exist two mechanisms, which control natriuretic peptide secretion. The first mechanism controls stretch-stimulated ANF secretion and is PTX-sensitive, while the second regulates basal ANF release and is PTX-insensitive. (Abstract shortened by UMI.)