Takahiro Horinouchi and Katsuo Koike*
Department of Chemical Pharmacology, Toho University School of Pharmaceutical
Sciences, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
*Corresponding author.ﾊﾊFAX:+81-47-472-1419
E-mail: ktkoike@phar.toho-u.ac.jp
Abstract: The properties of the b1-/b2-adrenoceptor
partial agonist carteolol were investigated in atypical b-adrenoceptors
on the guinea pig gastric fundus. Carteolol induced concentration-dependent
relaxation in this tissue (pD2=5.55, intrinsic activity=0.94).
However, a combination of the selective b1-adrenoceptor
antagonist atenolol (100ﾊmM) and the selective
b2-adrenoceptor antagonist butoxamine
(100ﾊmM) produced only small rightward shifts
in the concentration-response curves of carteolol in the gastric fundus
(pD2=4.91, intrinsic activity=0.94). In the presence of both
atenolol (100ﾊmM) and butoxamine (100ﾊmM),
the non-selective b1-, b2-
and b3-adrenoceptor antagonist (ｱ)-bupranolol
(10-100ﾊmM) caused a concentration-dependent
rightward shift of the concentration-response curves for carteolol in the
guinea pig gastric fundus. Schild plot analyses of the effects of (ｱ)-bupranolol
against carteolol gave the pA2 value of 5.29 and the Schild slope
was not significantly different from unity. Furthermore, carteolol (10ﾊmM)
weakly but significantly antagonized the relaxant responses to catecholamines
((-)-isoprenaline, (-)-noradrenaline and (-)-adrenaline), a selective b3-adrenoceptor
agonist BRL37344 ((R*,R*)-(ｱ)-4-[2-[(2-(3-chlorophenyl)-2-hydroxyethyl)amino]propyl]phenoxy
Keywords: Carteolol, Partial agonist, Atypical b-adrenoceptor,
b3-Adrenoceptor, Guinea pig gastric
fundus
Copyrightｩ The Japanese Pharmacological Society 2000
[Back to TOC]