Cholinergic-Adrenergic Dual Action of γ-Aminobutyric Acid Methylester on a Preparation of Toad's Sinus–Atrium

Abstract

THE effects of γ-aminobutyric acid methylester, NH₂(CH₂)₃COOCH₃ (I), its N-monomethyl (II), N-dimethyl (III) and N-trimethyl (IV) substituents were recently examined on the isolated heart of a toad by Takahashi¹. He reported the positive inotropic effect induced by (I) and (II), no effect by (III) and the negative inotropic effect by (IV). The induction of a quite opposite response by the difference of methyl moiety at the terminal nitrogen stimulated our interest to clarify the mode of action of these compounds. In this experiment a sinusatrium preparation of a toad's heart was used, of which double cannulæ were so constructed that the Ringer solution perfused thoroughly the inner surface of sinus and atrium. The inner cannula was attached through rubber tubes to Mariotte bottles which contained normal Ringer, atropine-Ringer (0.01 mg/ml.) and dichlorisoprenaline (DCI)-Ringer (0.02 mg/ml.) solution. Perfusion pressure was 20 cm water, and 0.1 ml. of the drug solution was injected into the tube to the cannula. Experiments were performed during September–October, 1961, and during February-March, 1962.