title: Alterations in rat aortic alpha 1-adrenoceptors and alpha 1-adrenergic stimulated phosphoinositide hydrolysis in intraperitoneal sepsis.
abstract: We investigated the alterations of rat aortic alpha 1-adrenoceptors and alpha 1-adrenergic stimulated phosphoinositide (PI) metabolism in intraperitoneal sepsis. An analysis of [125I]-hydroxyethylaminotetralone (HEAT) binding to alpha 1-adrenoceptors on rat aortic membranes revealed decreased numbers of receptors without changes in affinity. The maximum number of binding sites decreased from 349 +/- 35 fmol/mg to 146 +/- 16 fmol/mg (P less than 0.05 vs. control). PI metabolism was similarly attenuated in aortae from septic rats. The norepinephrine-stimulated hydrolysis of [32P]-phosphatidylinositol-4,5-bisphosphate was significantly decreased in aortae from septic rats as was the alpha 1-adrenoceptor stimulated accumulation of [3H]-inositol monophosphate. Finally, the basal labeling of [32P]-phosphatidylinositol-4,5-bisphosphate but not of [32P]-phosphatidylinositol or [32P]-phosphatidic acid was significantly diminished. These results imply that signal transduction induced by alpha 1-adrenoceptor agonists in rat aorta is significantly altered in intraperitoneal sepsis. These findings may help define the mechanisms of depressed aortic contractility in models of sepsis and endotoxic shock.
authors.affiliation: Naval Medical Research Institute, Bethesda, Maryland.
authors.forename: J A
authors.initials: JA
authors.lastname: Carcillo
authors.forename: R Z
authors.initials: RZ
authors.lastname: Litten
authors.forename: E A
authors.initials: EA
authors.lastname: Suba
authors.forename: B L
authors.initials: BL
authors.lastname: Roth
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D006868:Hydrolysis; D009638:Norepinephrine / Q000494:pharmacology; D010538:Peritonitis / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*
chemical_list: D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D011942:Receptors, Adrenergic, alpha; D009638:Norepinephrine