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) (ED50 = 18 microM), but did not affect the atrial rate (beta 1) or tracheal relaxation (beta 2) 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 beta 3-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.
Hioki
Y
Y
Tsukuba Research Institute Banyu Pharmaceutical Co., Ltd., Japan.
Itoh
Y
Y
Nakajima
A
A
Fukuroda
T
T
Ohasi
H
H
Kamei
T
T
Yano
M
M
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D007003:Hypoglycemia / Q000139:chemically induced*; D007583:Jejunum / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000187:drug effects
C100697:AZ 002; D005947:Glucose; D004837:Epinephrine