Biomaterial Database

Myocardial adenylate cyclase activity in acute murine Chagas' disease. 1988

S A Morris, and H Tanowitz, and S M Factor, and J P Bilezikian, and M Wittner

Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032.

We have studied the influence of myocardial infection with Trypanosoma cruzi on the beta-adrenergic adenylate cyclase complex in mouse myocardial membranes. The maximal rate of cAMP generation (Vmax) and the concentration of agonist associated with 50% of the maximal activity (apparent Kact) were determined for a series of agents. Six days after infection, the Vmax for isoproterenol significantly declines without a change in the apparent Kact. After 21 days of infection, both the Vmax and apparent Kact for isoproterenol are reduced. At 6 and 21 days of infection, the affinity of the beta-receptor for [125I]iodocyanopindolol declines from 0.84 to 3.6 and 3 nM, respectively, while the receptor density increases with the duration of infection from 33 to 57 and 82 fmol/mg protein, respectively. The Vmax (but not the apparent Kact) for forskolin and Mg2+- and Mn2+-associated activities declines also after 21 days. Another adenylate cyclase activity, which was stimulated by the nonhydrolyzable guanine nucleotide Gpp(NH)p, declines in relation to the duration of infection. Inhibitors of adenylate cyclase activity were also studied. Inhibition of adenylate cyclase activity by adenosine and by Gpp(NH)p (in the presence of forskolin) declines after 21 days of infection. The results suggested that the coupling proteins Ns and Ni, which mediate stimulatory or inhibitory control of receptors to adenylate cyclase activity, might be altered by infection. As monitored by cholera toxin- and pertussis toxin-dependent ADP ribosylation of their respective substrates, which include Ns and Ni proteins, respectively, there are declines in the availability of both substrates as a result of T. cruzi infection. For infected membranes, the addition of NADP enhances the magnitude of cholera toxin-dependent ADP ribosylation and renders the magnitude of pertussis toxin-dependent ADP ribosylation equal to that observed in uninfected membranes. The results support the hypothesis that infection with T. cruzi results in profound generalized alterations of the adenylate cyclase complex at several different sites.

UI	MeSH Term	Description	Entries
D008815	Mice, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.	Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D009206	Myocardium	The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.	Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D010566	Virulence Factors, Bordetella	A set of BACTERIAL ADHESINS and TOXINS, BIOLOGICAL produced by BORDETELLA organisms that determine the pathogenesis of BORDETELLA INFECTIONS, such as WHOOPING COUGH. They include filamentous hemagglutinin; FIMBRIAE PROTEINS; pertactin; PERTUSSIS TOXIN; ADENYLATE CYCLASE TOXIN; dermonecrotic toxin; tracheal cytotoxin; Bordetella LIPOPOLYSACCHARIDES; and tracheal colonization factor.	Bordetella Virulence Factors,Agglutinogen 2, Bordetella Pertussis,Bordetella Virulence Determinant,LFP-Hemagglutinin,LP-HA,Leukocytosis-Promoting Factor Hemagglutinin,Lymphocytosis-Promoting Factor-Hemagglutinin,Pertussis Agglutinins,Agglutinins, Pertussis,Determinant, Bordetella Virulence,Factor Hemagglutinin, Leukocytosis-Promoting,Factor-Hemagglutinin, Lymphocytosis-Promoting,Factors, Bordetella Virulence,Hemagglutinin, Leukocytosis-Promoting Factor,LFP Hemagglutinin,LP HA,Leukocytosis Promoting Factor Hemagglutinin,Lymphocytosis Promoting Factor Hemagglutinin,Virulence Determinant, Bordetella
D011943	Receptors, Adrenergic, beta	One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS.	Adrenergic beta-Receptor,Adrenergic beta-Receptors,Receptors, beta-Adrenergic,beta Adrenergic Receptor,beta-Adrenergic Receptor,beta-Adrenergic Receptors,Receptor, Adrenergic, beta,Adrenergic Receptor, beta,Adrenergic beta Receptor,Adrenergic beta Receptors,Receptor, beta Adrenergic,Receptor, beta-Adrenergic,Receptors, beta Adrenergic,beta Adrenergic Receptors,beta-Receptor, Adrenergic,beta-Receptors, Adrenergic
D002413	Cations, Divalent	Positively charged atoms, radicals or groups of atoms with a valence of plus 2, which travel to the cathode or negative pole during electrolysis.	Divalent Cations
D002598	Chagas Cardiomyopathy	A disease of the CARDIAC MUSCLE developed subsequent to the initial protozoan infection by TRYPANOSOMA CRUZI. After infection, less than 10% develop acute illness such as MYOCARDITIS (mostly in children). The disease then enters a latent phase without clinical symptoms until about 20 years later. Myocardial symptoms of advanced CHAGAS DISEASE include conduction defects (HEART BLOCK) and CARDIOMEGALY.	Cardiomyopathy, Chagas,Myocarditis, Chagas,Trypanosomiasis, Cardiovascular,Chagas' Cardiomyopathy,Cardiomyopathy, Chagas',Cardiovascular Trypanosomiasis
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D000067956	Adenylyl Cyclase Inhibitors	Compounds that bind to and inhibit the action of ADENYLYL CYCLASES.	Adenylate Cyclase Inhibitors,Cyclase Inhibitors, Adenylate,Cyclase Inhibitors, Adenylyl,Inhibitors, Adenylate Cyclase,Inhibitors, Adenylyl Cyclase
D000208	Acute Disease	Disease having a short and relatively severe course.	Acute Diseases,Disease, Acute,Diseases, Acute
D000242	Cyclic AMP	An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.	Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic