Research Information System
Pharmacology, vol.80, no.4, pp.227-238, 2007 (SCI-Expanded)
The contribution of β-adrenoceptor subtypes to the catecholamine-mediated relaxations in gastric fundus from control and streptozotocin (STZ)-induced diabetic rats were investigated. Isolated organ bath studies and molecular techniques were used to characterize the β-adrenoceptor subtypes mediating relaxation of rat gastric fundus. Isoprenaline-mediated relaxation was not significantly changed by nadolol (β1-/β2-adrenoceptor antagonist; 1 μmol/l) but only shifted to the right by SR59230A (3-(2-ethylphenoxy)-1-[[(1S)-1,2,3,4- tetrahydronaphth-1-yl]amino]-(2S)-2-propanol oxalate salt, 0.1-1 μmol/l), a selective β3-adrenoceptor antagonist, in a competitive manner. Relaxant responses to noradrenaline were antagonized in a concentration- dependent manner by SR59230A (0.1-1 μmol/l), but not by metoprolol (selective β1-adrenoceptor antagonist; 0.1-1 μmol/l) and ICI-118551 (1-[2,3-(dihydro-7-methyl-1Hinden- 4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride, selective β2-adrenoceptor antagonist; 0.1-1 μmol/l). SR59230A (1 μmol/l) also caused a significant rightward shift in fenoterol-induced relaxation while ICI-118551 (1 μmol/l) did not have any effect. Selective β3-adrenoceptor agonist, BRL37344 ([4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenoxy]acetic acid), caused biphasic relaxation which was not affected by nadolol (1 μmol/l). SR59230A (1 μmol/l) abolished only the first phase of BRL37344 response. β1-, β2- and β3-adrenoceptor mRNA expressions have been detected in a similar intensity in gastric fundus from control rats. Experimental diabetes caused a significant decrease in E max and pD2 values of isoprenaline and noradrenaline. Diabetes also reduced Emax but not pD2 value of the first component of BRL37344-induced relaxation response. The band intensity of mRNA transcript of β3-adrenoceptor was reduced in diabetics while no alteration has been found for β1- and β2- adrenoceptor mRNA transcripts between groups. These results show that functional β-adrenoceptor subtype involved in catecholamine-mediated relaxations is β3-adrenoceptor, and its function and mRNA expression are decreased in diabetes. Copyright © 2007 S. Karger AG.