Chagasic IgG stimulates phosphoinositide hydrolysis via neurotransmitter receptor activation: role of calcium.
Induction of polyphosphoinositide hydrolysis in cardiac tissue by IgG from chagasic mice was assayed. BALB/c mice auricles were labelled with myo-[3H]inositol precursor and inositol phosphate production in the presence or absence of chagasic IgG and the corresponding F(ab')2 was measured. Both chagasic IgG and F(ab')2 but not the normal forms specifically increased phosphoinositide turnover. This increment was blocked by muscarinic cholinergic antagonists and to an even greater extent by the phospholipase C inhibitor NCDC. Moreover, calcium channel blocking agents such as diltiazem, verapamil and D-600 also exerted an inhibitory action. A muscarinic cholinergic agonist, carbachol, and the ionophore A-23187, mimicked the action of the chagasic IgG upon phosphoinositide turnover. It is concluded that murine chagasic IgG and its F(ab')2 fragments result in stimulation of phospholipase C-mediated phosphoinositide hydrolysis through the interaction with muscarinic cholinergic receptors requiring the cytosolic calcium concentration to be raised.
Gorelik
G
G
Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Buenos Aires, Argentina.
Borda
E
E
Bacman
S
S
Cremaschi
G
G
Sterin-Borda
L
L
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D014355:Chagas Disease / Q000276:immunology*; D002850:Chromatography, Gel; D006868:Hydrolysis; D007140:Immunoglobulin Fab Fragments / Q000302:isolation & purification; D007074:Immunoglobulin G / Q000276:immunology* / Q000302:isolation & purification; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010716:Phosphatidylinositols / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000276:immunology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D002121:Calcium Channel Blockers; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D000001:Calcimycin; D010738:Type C Phospholipases; D002118:Calcium