Yoshio Hioki, Yoshiki Itoh, Akira Nakajima, Takahiro Fukuroda, Hiroshi Ohasi, Toshio Kamei and Mitsuo Yano
Tsukuba Research Institute Banyu Pharmaceutical Co., Ltd., Okubo 3, Tsukuba 300-33, Japan
Abstract: AZ002 (L-threo-(3,4-dihydroxy phenyl)-N-methyl serine methyl ester) is a newly synthesized adrenaline derivative. AZ002 caused relaxation of rat jejunum (beta3-receptors) (ED50=18 microM), but did not affect the atrial rate (beta1) or tracheal relaxation (beta2) at a concentration of 0.3 mM. The pA2 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 beta3-adrenoceptor. AZ002 stimulated lipolysis (ED50=10 microM) and glucose uptake (ED50=1 microM) 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.
Keywords: AZ002, Adrenaline derivative, beta3-Adrenoceptor, Adipocyte