AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 4 607-L614, Copyright © 1995 by American Physiological Society
Characterization of endothelin receptors in newborn piglet lung
T. Perreault and J. Baribeau
Department of Pediatrics, Montreal Children's Hospital, McGill University, Quebec, Canada.
Endothelins (ET-1, ET-2, and ET-3) cause dilation and constriction as a
result of binding to different ET receptors. ETA receptor is responsible
for the vasoconstrictor response, while ETB receptors lead to vasodilation
(ETB1) or vasoconstriction (ETB2). Although the effects of ETs have been
described in the neonatal pulmonary vasculature, ET receptors have not been
characterized extensively. Therefore, in newborn piglets we aimed to
characterize ET receptors by studying 1) in isolated perfused lungs the
effects of ET-1, ET-3, and the ETB receptor agonists sarafotoxin S6c (S6c)
and BQ-3020 on perfusion pressure with or without an ETA antagonist,
BQ-123, or an ETB1 antagonist, RES-701-1, and 2) the
concentration-dependence of ET-1 and ET-3 on their binding to microsomes
from arteries and veins of piglet lungs. ET-1, ET-3, S6c, and BQ-3020 cause
an early-onset dilation followed by a late-onset constriction. The dilator
response to ET-3 is blunted by RES-701-1 (P < 0.005), while the
inhibition of the dilator response of ET-1 almost reaches significance (P =
0.06). BQ-123 inhibits incompletely (P < 0.05) the constrictor response
to ET-1, while it does not alter the response to ET-3. This suggests that
constriction may follow binding to ETA as well as ETB2 receptors. Binding
studies reveal that ET receptors are abundant in pulmonary vessels. ETA
receptors are predominant, but ETB1 and likely ETB2 receptors are also
present. Also, receptor affinities are higher in veins than in
arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
