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Diabetic KK-CAy 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 (10 mg/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 (100 micrograms/kg, i.p.), a beta 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 30 s 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 beta 1-adrenergic sensitive mice may be stratified into two groups based upon an antagonistic interaction between higenamine and aconitine.

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Two Groups of Diabetic KK-CAy Mice Specifically Bred for High and Low Sensitivity to Exogenous Acetylcholine and .BETA.1-Adrenergic Stimulation: Interaction of Higenamine and Aconitine on Pulse Rate.