2 GROUPS OF DIABETIC KK-CA(Y) MICE SPECIFICALLY BRED FOR HIGH AND LOW-SENSITIVITY TO EXOGENOUS ACETYLCHOLINE AND BETA(1)-ADRENERGIC STIMULATION - INTERACTION OF HIGENAMINE AND ACONITINE ON PULSE-RATE

Diabetic KK-CA(y) mice were specifically bred for high and low sensiti vity to the addition of exogenous acetylcholine (ACh). The sensitivity to ACh was measured by the change in pulse rate 2 min after the admin istration of ACh (10 mg/kg, s.c.), The two groups of mice, with high a nd low sensitivity to ACL, were specially selected and mated sequentia lly until the 12th filial generation. Although higenamine (100 mu g/kg , i.p.), a beta(1)-adrenergic agonist (a compound derived from aconite ), had no effect per se, it inhibited aconitine (another compound deri ved from aconite extract)-induced bradycardia within 30s of administra tion in ACh-low sensitive mice but not in ACh-high sensitive mice. The effects of aconitine and higenamine alone did not differ between thes e two groups of mice. This demonstrates that the high muscarinic and h igh beta(1)-adrenergic sensitive mice may be stratified into two group s based upon an antagonistic interaction between higenamine and aconit ine.