title: Smooth muscle guanine nucleotides and receptor-effector coupling following inhibition of oxidative energy production.
abstract: We measured total concentrations of guanosine triphosphate (GTP) and guanosine diphosphate (GDP) in rabbit aortic smooth muscle under several different conditions. We computed free [GDP] and free GTP/GDP (using a Keq of 1.0 for the nucleoside diphosphate kinase reduction) under these conditions. At a time when muscle was contracted by 15 microM norepinephrine (NE) for 5 min under normoxia, [GTP], free [GDP], and free GTP/GDP were 0.29 +/- 0.03 mM, 3.5 microM, and 82, respectively. Following rapid inhibition of oxidative energy production during NE-evoked maintained force, which is associated with slow decreases in mean tissue [PCr], and [ATP] and force relaxation, [GTP] and free GTP/GDP were decreased at relaxation threshold to 0.22 +/- 0.02 (SE) mM and 43, respectively, and progressively fell further, paralleling decreases in force and [ATP] and [PCr]. There were marked decreases in the sum of GTP + GDP contents under conditions where muscle energy stores were decreased (i.e., low [PCr] + [ATP]). Similar data were obtained during a 50 mM KCl-evoked contracture. Free [GDP] increased from normoxic values of 3.5 microM to values as great as 6.0 microM at low energy store states. Free GDP was equivalent to 6% of total GDP under normoxia and increased to 16-21% of total GDP under conditions of low energy stores. Evidence was obtained that decreases in [GTP] or free GTP/GDP seen under conditions of low total energy stores were not sufficient to inhibit heterotrimeric G protein function and uncouple receptor-effector coupling.
authors.affiliation: Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia 19104.
authors.forename: R F
authors.initials: RF
authors.lastname: Coburn
authors.forename: S
authors.initials: S
authors.lastname: Azim
authors.forename: W S
authors.initials: WS
authors.lastname: Fillers
authors.forename: C B
authors.initials: CB
authors.lastname: Baron
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010084:Oxidation-Reduction; D010725:Phosphocreatine / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D014661:Vasoconstriction; D014664:Vasodilation
chemical_list: D010725:Phosphocreatine; D006153:Guanosine Diphosphate; D011189:Potassium Chloride; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D009638:Norepinephrine