PT  - JOURNAL ARTICLE
AU  - Piascik, M T
AU  - Guarino, R D
AU  - Smith, M S
AU  - Soltis, E E
AU  - Saussy, D L
AU  - Perez, D M
TI  - The specific contribution of the novel alpha-1D adrenoceptor to the contraction of vascular smooth muscle.
DP  - 1995 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1583--1589
VI  - 275
IP  - 3
4099  - http://jpet.aspetjournals.org/content/275/3/1583.short
4100  - http://jpet.aspetjournals.org/content/275/3/1583.full
SO  - J Pharmacol Exp Ther1995 Dec 01; 275
AB  - With a selective antagonist, the specific contribution of the alpha-1D adrenoceptor (AR) to vascular smooth muscle contraction has been assessed. BMY 7378 bound to membranes expressing the cloned rat alpha-1D AR with a > 100-fold higher affinity (K1 = 2 nM) than binding to either the cloned rat alpha-1A AR (Ki = 800 nM) or the hamster alpha-1B AR (Ki = 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 < 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.