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.
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.
Kimura
I
I
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Makino
M
M
Honda
R
R
Kimura
M
M
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology*; D000157:Aconitine / Q000494:pharmacology; D058665:Adrenergic beta-1 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001341:Autonomic Nervous System / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D011674:Pulse / Q000187:drug effects*; D044005:Tetrahydroisoquinolines
D058665:Adrenergic beta-1 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000470:Alkaloids; D044005:Tetrahydroisoquinolines; D000109:Acetylcholine; C012348:higenamine; D000157:Aconitine