Cholinergic response of isolated rat atria to recombinant rat interferon-gamma.
Addition of recombinant rat interferon-gamma (IFN-gamma) to beating rat atria decreased the contractile strength in a dose-dependent manner. The effect was specific of IFN-gamma since it was abrogated by monoclonal anti-rat IFN-gamma. It required the activation of the cholinergic system of the heart as inhibition of both nicotinic (10(-7) M hexametonium) and muscarinic cholinoceptors (10(-7) M atropine) prevented the reaction. Hemicholinium (2 x 10(-5) M) and tetrodotoxin (5 x 10(-7) M) also reduced the response. Likewise, IFN-gamma potentiated the action of the muscarinic agonist carbachol. IFN-gamma simulated the biological effect of cholinergic agonists because: (a) it increased cGMP formation; (b) it decreased cAMP formation; and (c) it reduced heart contractility at doses that can be considered physiologic. IFN-gamma also modified the muscarinic receptor by interfering with the binding of the radiolabelled antagonist quinuclidinyl benzilate [( 3H]QNB). It is suggested that IFN-gamma binding to IFN-gamma receptors in the heart may lead to a cholinergic response by interaction of both receptor systems on the surface of atrial cells.
Borda
E
E
CEFAPRIN-CONICET, Buenos Aires, Argentina.
Leirós
C P
CP
Sterin-Borda
L
L
de Bracco
M M
MM
D000818:Animals; D001667:Binding, Competitive; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006325:Heart Atria; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009712:Nucleotides, Cyclic / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011994:Recombinant Proteins
D009712:Nucleotides, Cyclic; D011950:Receptors, Cholinergic; D011994:Recombinant Proteins; D011813:Quinuclidinyl Benzilate; D007371:Interferon-gamma