Two Groups of Diabetic KK-CA^y Mice Specifically Bred for High and Low Sensitivity to Exogenous Acetylcholine and β_1-Adrenergic Stimulation : Interaction of Higenamine and Aconitine on Pulse Rate

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Diabetic KK-CA^y mice were specifically bred for high and low sensitivity to the addition of exogenous acetylcholine (ACh). The sensitivity to ACh was measured by the change in pulse rate 2 min after the administration of ACh (10mg/kg, s.c.). The two groups of mice, with high and low sensitivity to ACh, were specially selected and mated sequentially until the 12th filial generation. Although higenamine (100μg/kg, i.p.), a β_1-adrenergic agonist (a compound derived from aconite), had no effect per se, it inhibited aconitine (another compound derived from aconite extract)-induced bradycardia within 30s of administration in ACh-low sensitive mice but not in ACh-high sensitive mice. The effects of aconitine and higenamine alone did not differ between these two groups of mice. This demonstrates that the high muscarinic and high β_1-adrenergic sensitive mice may be stratified into two groups based upon an antagonistic interaction between higenamine and aconitine.
公益社団法人日本薬学会の論文
1995-10-15