PT  - JOURNAL ARTICLE
AU  - Sandra L. Hrometz
AU  - Stephanie E. Edelmann
AU  - Dan F. McCune
AU  - Jennifer R. Olges
AU  - Robert W. Hadley
AU  - Dianne M. Perez
AU  - Michael T. Piascik
TI  - Expression of Multiple α<sub>1</sub>-Adrenoceptors on Vascular Smooth Muscle: Correlation with the Regulation of Contraction
DP  - 1999 Jul 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 452--463
VI  - 290
IP  - 1
4099  - http://jpet.aspetjournals.org/content/290/1/452.short
4100  - http://jpet.aspetjournals.org/content/290/1/452.full
SO  - J Pharmacol Exp Ther1999 Jul 01; 290
AB  - Previous work has shown that the genes encoding each α1-adrenoceptor subtype are coexpressed throughout the peripheral vascular system. We have evaluated subtype-selective antibodies as tools to determine the extent of protein expression in arteries. The α1A-, α1B-, and α1D-adrenoceptors were detected in the medial layer of the aorta, caudal, femoral, iliac, renal, superior mesenteric, and mesenteric resistance arteries. In Rat1 fibroblasts expressing each subtype, immunoreactivity was noted both on the cell surface and in a perinuclear orientation. Intense α1B-adrenoceptor immunostaining was similarly localized in cultured femoral and renal vascular smooth muscle cells. Although the cellular localization appeared to be the same, immunoreactivity obtained with α1A- and α1D-adrenoceptors was much less intense than that with the α1B-adrenoceptor. The α1A-adrenoceptor selective agonist A-61603 was 22-fold more potent in activating renal artery contraction when compared with the femoral artery. The expression of each α1-adrenoceptor was significantly decreased by in vivo application of antisense oligonucleotides targeted against each subtype. Inhibition of the expression of only one, the α1A in renal and the α1D in femoral arteries, reduced the contractile response to naphazoline. The results show: 1) subtype-selective antibodies can be used in tissues and cell culture to localize the α1-adrenoceptor subtypes, 2) in addition to expression on the cell surface, the α1-adrenoceptors are expressed intracellularly, and 3) despite expression of all adrenoceptors, a single subtype mediates the contractile response in the femoral and renal arteries. The American Society for Pharmacology and Experimental Therapeutics