Modulation of cardiac physiology by an anti-Trypanosoma cruzi monoclonal antibody after interaction with myocardium. 1995

G Cremaschi, and N W Zwirner, and G Gorelik, and E L Malchiodi, and M G Chiaramonte, and C A Fossati, and L Sterin-Borda
Centro de Estudios Farmacológicos y Botánicos (CEFYBO-CONICET), Buenos Aires, Argentina.

Circulating antibodies from human and murine chagasic sera are able to interact with myocardium, activating neurotransmitter receptors. Here, we studied the effects of a monoclonal antibody (MAb CAK20.12), which recognizes a 150 kilodalton antigen of Trypanosoma cruzi and reacts with normal human and murine striated muscles and with cardiac tissue. The MAb CAK20.12 binds to purified cardiac membranes and interferes with the binding of beta-adrenergic receptor radioligand ([125I]CYP) and muscarinic cholinergic receptor (mAChR) radioligand ([3H]QNB) in a noncompetitive way. As a consequence of this interaction, beta-adrenergic receptor and mAChR were activated, leading to increased intracellular levels of cyclic AMP as a result of beta-adrenergic receptor-coupled adenylate cyclase triggering. When its sympathetic action was abrogated, it also induced an mAChR-mediated increase in cyclic GMP. Furthermore, cardiac physiology was modified by MAb CAK20.12, as it was able to increase cardiac contractility through beta-adrenoceptor activation and to decrease atrial frequency as a result of mAChR activation. The fact that this MAb modulates and modifies the mechanical and biochemical activity of normal murine heart established an important basis for future research and understanding of how the host's humoral immune response acts on the course and development of the chronic chagasic myocardiopathy.

UI MeSH Term Description Entries
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D009200 Myocardial Contraction Contractile activity of the MYOCARDIUM. Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
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
D010869 Pindolol A moderately lipophilic beta blocker (ADRENERGIC BETA-ANTAGONISTS). It is non-cardioselective and has intrinsic sympathomimetic actions, but little membrane-stabilizing activity. (From Martindale, The Extra Pharmocopoeia, 30th ed, p638) Prindolol,LB-46,Visken,LB 46,LB46
D011813 Quinuclidinyl Benzilate A high-affinity muscarinic antagonist commonly used as a tool in animal and tissue studies. Benzilate, Quinuclidinyl
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
D006152 Cyclic GMP Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed) Guanosine Cyclic 3',5'-Monophosphate,Guanosine Cyclic 3,5 Monophosphate,Guanosine Cyclic Monophosphate,Guanosine Cyclic-3',5'-Monophosphate,3',5'-Monophosphate, Guanosine Cyclic,Cyclic 3',5'-Monophosphate, Guanosine,Cyclic Monophosphate, Guanosine,Cyclic-3',5'-Monophosphate, Guanosine,GMP, Cyclic,Guanosine Cyclic 3',5' Monophosphate,Monophosphate, Guanosine Cyclic
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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

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