A NOVEL ADRENALINE DERIVATIVE, AZ002, AND ITS HYPOGLYCEMIC ACTION IN YELLOW KK MICE

AZ002 (L-threo-(3,4-dihydroxy phenyl)-N-methyl serine methyl ester) is a newly synthesized adrenaline derivative. AZ002 caused relaxation of rat jejunum (beta(3)-receptors) (ED(50) = 18 mu M), but did not affect the atrial rate (beta(1)) or tracheal relaxation (beta(2)) at a concentration of 0.3 mM. The pA(2) values for propranolol in inhibiting the isoproterenol- and AZ002-stimulated relaxation of rat jejunum were 6.27 and 6.33, respectively. Thus, AZ002 is a selective agonist for beta(3)-adrenoceptor. AZ002 stimulated lipolysis (ED(50) = 10 mu M) and glucose uptake (ED(50) = 1 mu M) in rat adipocytes. In both cases, stimulation was antagonized by high concentrations of the beta-adrenoceptor antagonist propranolol, but not by the alpha-adrenoceptor antagonist phentolamine. The effect of AZ002 on glucose uptake was synergistic with that of insulin. AZ002 was also assessed in vivo by using genetically obese mice (KK/Ay strain) with hyperglycemia. Administration of AZ002 in the diet for a week decreased blood glucose and non-esterified fatty acids.