Pregnancy markedly increases endothelin-1-induced contraction and
changes receptor subtypes in uterine smooth muscle in humans.
Fujita, Kayo, Hajime Tsunoda, Takashi Miyauchi, Yasuro Sugishita,
Takeshi Kubo, and Katsutoshi Goto.
Department of Obstetrics and Gynecology, Department of Internal
Medicine (Division of Cardiology), Institute of Clinical Medicine and
Department of Pharmacology, Institute of Basic Medical Sciences,
University of Tsukuba, Tsukuba-shi, Ibaraki 305, Japan
APStracts 3:0357R, 1996.
The purpose of the present study was to investigate whether pregnancy
affects endothelin (ET)-1-induced contraction, the density of ET
receptors and the ratio of receptor subtypes (ETA and ETB) in uterine
smooth muscle in humans. We also investigated which ET receptor
subtypes mediate ET-1-induced contraction in the human uterus. In
uterine membrane preparations, [125I]ET-1 binding sites (Bmax) in
pregnant women did not differ from those in age-matched non-pregnant
women (596.2 [umlaut]u} 107.1 vs 512.1 [umlaut]u} 167.7fmol/mg
protein). The dissociation constant (Kd) in pregnant women did not
differ from that in non-pregnant women. Competitive displacement
experiments with [125I]ET-1 binding to the membranes using BQ-123
(ETA receptor antagonist) showed that the percentage of ETA receptors
in uterine muscle was significantly higher in pregnant women than in
non-pregnant women (P<0.01). The calculated ratios of ETA to
ETB receptors in pregnant and non-pregnant uteri were 92 : 8 and 68 :
32, respectively. Combination treatment with BQ-788(ETB receptor
antagonist) completely inhibited the BQ-123-resistant component of
[125I]ET-1 specific binding. ET-1 caused dose-dependent contractions
in isolated human uteri from both pregnant and non-pregnant women.
The maximum response was markedly greater in pregnant women than in
non-pregnant women, while pD2 values did not differ between pregnant
and non-pregnant uteri. In pregnant human uterus, BQ-123 (10-6M)
significantly shifted the dose-dependent curve of ET-1 response to
the right, while BQ-3020 (ETB receptor agonist) did not cause
contraction. These results suggested that ET-1-induced contraction of
the human uterus is mediated through only ETA receptors and that ET
-1-induced uterine contraction in humans is markedly increased during
pregnancy. In addition, the present study suggests that, although
[125I]ET-1 binding sites (Bmax) are not altered during pregnancy, the
proportion of ETA receptors is increased and that of ETB receptors is
decreased in the pregnant human uterus.
Received 13 November 1995; accepted in final form 3 September
1996.
APS Manuscript Number R708-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996