title: Transmembrane mechanochemical coupling in cardiac myocytes: novel activation of Gi by hyposmotic swelling.
abstract: We have studied the effect of hyposmotic swelling on adenosin 3',5'-cyclic monophosphate (cAMP) metabolism in isolated cardiac myocytes. Decreasing extracellular osmolarity by 12.5-50% results in graded inhibition (10-40%) of isoproterenol-stimulated and forskolin-stimulated cAMP accumulation but does not affect basal and hormone-stimulated phosphoinositide hydrolysis or cellular ATP content. Treatment with pertussis toxin does not alter the swelling response but abolishes the inhibitory effect of swelling on cAMP accumulation. The response to swelling seems not to involve the release of effectors known to couple to inhibitory G protein (Gi) in myocytes: BQ-123, atropine, and adenosine deaminase do not alter the inhibitory effect of swelling on isoproterenol-stimulated cAMP accumulation; conditioned medium from swollen cells, with restored osmolarity, has no effect on cAMP accumulation when added to control myocytes. In distinction to these effects on myocytes, swelling enhances hormone-stimulated cAMP accumulation in cultured S49 lymphoma cells. We conclude that swelling of cardiac myocytes inhibits cAMP accumulation through a mechanism that involves activation of a pertussis toxin-sensitive Gi protein. Activation of Gi by this means may contribute to adrenergic hyporesponsiveness in hypoxic and ischemic myocardium.
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla 92093, USA.
authors.forename: R
authors.initials: R
authors.lastname: Hilal-Dandan
authors.forename: L L
authors.initials: LL
authors.lastname: Brunton
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D008223:Lymphoma / Q000378:metabolism / Q000473:pathology; D008566:Membranes / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009997:Osmotic Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D019204:GTP-Binding Proteins