离体大鼠心房对重组大鼠干扰素-γ的胆碱能反应。

Cholinergic response of isolated rat atria to recombinant rat interferon-gamma.

作者信息

Borda E, Leirós C P, Sterin-Borda L, de Bracco M M

机构信息

CEFAPRIN-CONICET, Buenos Aires, Argentina.

出版信息

J Neuroimmunol. 1991 Apr;32(1):53-9. doi: 10.1016/0165-5728(91)90071-e.

DOI:10.1016/0165-5728(91)90071-e

PMID:1900518

Abstract

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.

摘要

向跳动的大鼠心房添加重组大鼠干扰素-γ（IFN-γ）会以剂量依赖的方式降低收缩强度。该效应具有IFN-γ特异性，因为它可被抗大鼠IFN-γ单克隆抗体消除。它需要激活心脏的胆碱能系统，因为抑制烟碱样（10⁻⁷M六甲铵）和毒蕈碱样胆碱能受体（10⁻⁷M阿托品）均可阻止该反应。半胱胺（2×10⁻⁵M）和河豚毒素（5×10⁻⁷M）也会降低反应。同样，IFN-γ增强了毒蕈碱样激动剂卡巴胆碱的作用。IFN-γ模拟了胆碱能激动剂的生物学效应，因为：（a）它增加了环鸟苷酸（cGMP）的形成；（b）它减少了环磷酸腺苷（cAMP）的形成；（c）它在可被视为生理剂量时降低了心脏收缩力。IFN-γ还通过干扰放射性标记拮抗剂喹核醇基苯甲酸酯[³H]QNB的结合来修饰毒蕈碱样受体。有人提出，IFN-γ与心脏中的IFN-γ受体结合可能通过心房细胞表面两种受体系统的相互作用导致胆碱能反应。