Faculty Collaboration Database

Decrease in vascular TxA2 receptors in a subgroup of rabbits unresponsive to a TxA2 mimetic. Am J Physiol 1994 Jun;266(6 Pt 2):H2320-6

Date

06/01/1994

Pubmed ID

8023992

DOI

10.1152/ajpheart.1994.266.6.H2320

Scopus ID

2-s2.0-0028451606 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

In rabbit pulmonary artery, endothelium-dependent contractions to arachidonic acid and methacholine are mediated by thromboxane (Tx) A2. The TxA2 mimetics U-46619 and (1S-[1 alpha,2 beta(5Z),3 alpha(1E,3R*),4 alpha])-7-[3- [3-hydroxy-4-(4'-iodophenoxy)-1-butenyl]-7-oxabicyclo(2.2.1)hep tan-2-yl]- 5-heptenoic acid (I-BOP), norepinephrine, and endothelin produced endothelium-independent contractions. Arachidonic acid, methacholine, U-46619, and I-BOP failed to produce contractions in a subgroup of rabbits (25%). Nonresponder arteries contracted similarly to norepinephrine and endothelin as responder arteries. The affinity (Kd) and density (Bmax) of TxA2 receptors in crude pulmonary artery membranes were assessed via equilibrium binding studies using 125I-BOP. There was no difference in Kd between the two groups (0.49 +/- 0.17 vs. 0.32 +/- 0.14 nM, responder vs. nonresponder). There was a significant decrease in Bmax (123 +/- 21 vs. 28 +/- 11 fmol/mg protein, responder vs. nonresponder; P < 0.01) of receptors in the nonresponders. Nonresponder aortas also did not contract to U-46619 and exhibited a decrease in TxA2 receptors, indicating that the difference is not specific for the pulmonary artery. Nonresponder platelets aggregated to U-46619, suggesting that the platelet receptor is not altered. TxA2-receptor expression may be regulated in vivo. Nonresponder rabbits may provide a useful model for studying these receptors in vascular disease.

Author List

Buzzard CJ, Pfister SL, Halushka PV, Campbell WB

Authors

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Sandra L. Pfister PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Arachidonic Acid
Drug Resistance
Endothelium, Vascular
Hormones
Male
Platelet Aggregation
Pulmonary Artery
Rabbits
Radioligand Assay
Receptors, Thromboxane
Thromboxane A2
Vasoconstrictor Agents