Cholinergic response of isolated rat atria to recombinant rat interferon-γ

Abstract

Addition of recombinant rat interferon-γ (IFN-γ) to beating rat atria decreased the contractile strength in a dose-dependent manner. The effect was specific of IFN-γ since it was abrogated by monoclonal anti-rat IFN-γ. 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 (2×10 −5 M) and tetrodotoxin (5×10 −7 M) also reduced the response. Likewise, IFN-γ potentiated the action of the muscarinic agonist carbachol. IFN-γ 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-γ also modified the muscarinic receptor by interfering with the binding of the radiolabelled antagonist quinuclidinyl benzilate ([ 3H]QNB). It is suggested that IFN-γ binding to IFN-γ receptors in the heart may lead to a cholinergic response by interaction of both receptor systems on the surface of atrial cells.