IMMUNOCYTOCHEMICAL LOCALIZATION OF THE ALPHA-1B ADRENERGIC-RECEPTOR AND THE CONTRIBUTION OF THIS AND THE OTHER SUBTYPES TO VASCULAR SMOOTH-MUSCLE CONTRACTION - ANALYSIS WITH SELECTIVE LIGANDS AND ANTISENSE OLIGONUCLEOTIDES

The contribution of the alpha-1B adrenergic receptor (AR) to vascular smooth muscle contraction has been assessed using a combination of imm unological, molecular biological and pharmacological approaches. A sub type-selective antibody detected alpha-1B immunoreactivity in the medi al layer of the aorta, caudal, femoral, iliac, mesenteric resistance, renal and superior mesenteric arteries. Receptor protection assays and antisense oligonucleotides were used to assess the contribution of th e alpha-1B AR to contraction. The alpha-1B AR was implicated in mediat ing the phenylephrine-induced contraction of the mesenteric resistance artery. The alpha-1D AR was implicated in mediating the contraction o f the aorta, femoral, iliac and superior mesenteric arteries. Similarl y, the alpha-1A AR was implicated in mediating contraction of the caud al and renal arteries. In vivo application of antisense oligonucleotid es targeted to the translational start Site of the alpha-1B AR had no effect on the phenylephrine-induced contraction of the femoral or rena l arteries. In contrast, antisense oligonucleotides directed against t he alpha-1D AR significantly inhibited the phenylephrine response in t he femoral artery but had no effect on the renal artery. Application o f alpha-1A AR antisense oligonucleotides inhibited the contraction of the renal artery without effect on the femoral artery. These data show that (1) alpha-1B AR immunoreactivity is widely distributed in the sa me peripheral arteries in which previous studies detected its mRNA, an d (2) despite this distribution, receptor protection and antisense oli gonucleotide studies indicate that the alpha-1B AR mediates the contra ction of only the mesenteric resistance artery.