Chronic sympathectomy of canine cardiac ventricles affects Gs-adenylyl cyclase coupling and muscarinic receptor density

Eugene E. Quist, Shang Chiun Lee, Ranga Vasan, Brian Foresman, Patricia Gwirtz, Carl E. Jones

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

The effect of chronic ventricular sympathectomy on sarcolemmal muscarinic receptor (MR) and β-adrenoceptor densities and coupling of these receptors to adenylyl cyclase was examined. Microsomal membranes were isolated from right and left ventricles of control dogs (sham- and nonoperated) and dogs with ventricles sym-pathectomized 4 weeks earlier. Relative to control membranes, MR density was decreased in left but not right ventricular (LV, RV) membranes from sympathecto-mized hearts. Relative carbachol inhibition of adenylyl cyclase was similar in RV and LV membranes from both heart groups, however. Although β-adrenoceptor densities and ratio of β1- and β2-adrenoceptor subtypes did not change, basal adenylyl cyclase activity was 40% less in sympathectomized membranes as compared with control membranes. Furthermore, relative stimulation of adenylyl cyclase by isoproterenol was twofold greater in sym-pathectomized heart membranes. Because maximally stimulated adenylyl cyclase activity by NaF or MnCl2was identical in sympathectomized and control membranes, the reduction in basal activity may not be related to a decrease in Gsand adenylyl cyclase. In support of this hypothesis, Gcontent as estimated from optimal cholera toxin-catalyzed ADP-ribosylation was similar in control and sympathectomized membranes. Therefore, an alteration in Gsinteraction with adenylyl cyclase may account for the reduction in basal adenylyl cyclase activity and the increased relative responsiveness of adenylyl cyclase to isoproterenol in chronically sympathectomized ventricular membranes.

Original languageEnglish
Pages (from-to)936-943
Number of pages8
JournalJournal of Cardiovascular Pharmacology
Volume23
Issue number6
DOIs
StatePublished - Jun 1994

Keywords

  • Adenyl cyclase activity
  • G
  • Muscarinic receptor
  • Ventricular sympathectomy
  • β-Adrenoceptor

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