Characterization of subtype of alpha(1)-adrenoceptor mediating vasoconstriction in perfused rat mesenteric vascular bed

Citation
Wz. Zhu et al., Characterization of subtype of alpha(1)-adrenoceptor mediating vasoconstriction in perfused rat mesenteric vascular bed, ACT PHAR SI, 20(2), 1999, pp. 151-156
Citations number
14
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
ACTA PHARMACOLOGICA SINICA
ISSN journal
0253-9756 → ACNP
Volume
20
Issue
2
Year of publication
1999
Pages
151 - 156
Database
ISI
SICI code
0253-9756(199902)20:2<151:COSOAM>2.0.ZU;2-5
Abstract
AIM: To characterize the subtype of alpha(1)-adrenoceptor mediating vasocon striction in perfused rat mesenteric vascular bed. METHODS: The potencies ( pA(2) values determined by Schild plot) of alpha(1)-adrenoceptor-selective antagonists were determined by isolated vasoconstrictive experiment. The pK (i) values were determined by I-125-BE 2254 binding from the cloned alpha(1 A)-, alpha(1B)-, and alpha(1D)-adrenoceptor, stably expressed in human embr yonic kidney (HEK) 293 cells. RESULTS: The pA(2) values for alpha(1A)-adren oceptor-selective antagonists, RS-17053, WB 4101, 5-methyl-urapidil, and th e alpha(1D)-adrenoceptor-selective antagonist, BMY 7378, were 8.98 +/- 0.28 , 9.16 +/- 0.20, 8.69 +/- 0.02, and 6.03 +/- 0.26, respectively, with the s lope not different from unity. The pA(2) values of the above antagonists co rrelated well with the binding pK(i) values only for alpha(1A)-adrenoceptor s (r = 0.97), but not for alpha(1B)-adrenoceptors (r = 0.52) and alpha(1D)- adrenoceptors (r = 0.04). The concentration-vasopressor response curve for norepinephrine was not affected by pretreatment with chloroethylclonidine ( Chl) 50 mu mol.L-1 for 30 min. CONCLUSION: Only alpha(1A)-adrenoceptors med iate the norepinephrine-induced vasopressor response in perfused rat mesent eric vascular bed.