The specific contribution of the novel alpha-1D adrenoceptor to the contraction of vascular smooth muscle
Piascik, M.T.; Guarino, R.D.; Smith, M.S.; Soltis, E.E.; Saussy, D.L.; Perez, D.M.
Journal of Pharmacology and Experimental Therapeutics 275(3): 1583-1589
1995
ISSN/ISBN: 0022-3565 PMID: 8531132 Document Number: 447600
With a selective antagonist, the specific contribution of the alpha-1 D adrenoceptor (AR) to vascular smooth muscle contraction has been assessed. BMY 7378 bound to membranes expressing the cloned rat alpha-1D AR with a gt 100-fold higher affinity (K-1 = 2 nM) than binding to either the cloned rat alpha-1A AR (K-i = 800 nM) or the hamster alpha-1B AR (K-i = 600 nM). BMY 7378 exhibited differential potency in inhibiting vascular smooth muscle contraction. In the rat aorta and iliac artery, BMY 7378 was a high-affinity antagonist, producing parallel shifts in the phenylephrine concentration-response curve. The dissociation constants for this compound by Schild analysis were 0.95 and 4 nM for the aorta and iliac artery, respectively. The slopes of these Schild plots were not significantly different from unity. BMY 7378 was a weak antagonist in the rat caudal, mesenteric resistance and renal arteries, with Schild slopes significantly lt 1. With ribonuclease protection assays, alpha-1D mRNA was found in all blood vessels examined. These data suggest that (1) BMY 7378 is a selective alpha-1D AR antagonist that can be used in functional systems to assess the contribution of this receptor in vascular smooth muscle contraction; (2) the alpha-1D AR appears to play a major role in the contraction of the aorta and iliac artery; (3) despite the fact that the mRNA for the alpha-1D AR can be detected in the caudal, mesenteric resistance (4) and renal arteries, it does not appear to play a role in mediating contraction of these blood vessels; and (4) expression of alpha-1D mRNA in a particular artery does not ensure that this receptor is involved in regulating the contraction of that artery.