Human syncytiotrophoblast npy receptors are located on brush border
membranes and activate the phospholipase c to protein kinase c
axis.
Robidoux, Jacques, Lucie Simoneau, Serge St-Pierre, Hafid Ech-Chadli,
and Julie Lafond.
D[acute]epartement d'Obst[acute]etrique-Gyn[acute]ecologie,
Facult[acute]e de m[acute]edecine, Universit[acute]e de
Montr[acute]eal, D[acute]epartement des Sciences Biologiques and de
Chimie, Universit[acute]e du Qu[acute]ebec [grave]a Montr[acute]eal,
Montr[acute]eal (Canada) Canada, H3C 3P8
APStracts 4:0279E, 1997.
Neuropeptide Y (NPY) is abundant in plasma and amniotic fluid of women
throughout pregnancy, during which, its involvement in placental
hormonogenesis has been proposed. In accordance to its putative role,
the aim of this study was to characterize the human placental
syncytiotrophoblast receptivity to NPY. Thus, we performed this study
on brush border membranes (BBM) and basal plasma membranes (BPM).
Specific [125I]NPY binding to BBM was rapid (20 min), saturable with
a Bmax of 604 +/- 100 fmol/mg protein and of high affinity with a KD
of 11 +/- 3 nM. No saturable binding could be shown in BPM. The rank
order of NPY and related peptides affinity to compete for [125I]NPY
binding sites was: PYY > NPY = [Leu31, Pro34]-NPY > 13-36NPY
>> PP. It is noteworthy that PYY displaced only 45% of the
binding sites. In BBM, both NPY and PYY were potent phospholipase C
(PLC) stimulators, leading to a 4-5 fold increase of control
phosphodiesterase activity. The later effect could be prevented by
preincubation of membranes with 5 [mu]M U-73122, a known inhibitor of
G-protein-linked receptors activation of PLC-[beta]. Furthermore, 5
[mu]M BIBP3226 a Y1 receptor antagonist, shifted both dose-response
curves to the right in a similar fashion for both peptides. In
accordance with the PLC stimulation, both peptides also induced
stimulation of protein kinase C (PKC) activity, which could be
partially but additively prevented by U-73122 and LY294002 a
selective inhibitor of phosphatidylionositol-3 kinase (PI3K). Taken
together, these data suggest that placental and blood derived NPY
bind to a mixed population of receptors composed of Y1- and Y3
-subtype on the maternal side of the syncytiotrophoblast, where it
could mediate its physiological purposes, via the PLC-[beta] and PI3K
activation, both of which, lead to PKC activation. However, since
BIBP3226 antagonized both effects, the physiological relevance of the
apparent Y3 fraction is still unsolved.
Received 29 May 1997; accepted in final form 10 December 1997.
APS Manuscript Number E247-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 January 1998