Neuropeptide y reduces macromolecule permeability of coronary
endothelial monolayers.
Noll, T., A. Hempel, H. M. Piper.
Physiologisches Institut, Justus-Liebig-Universit[umlaut]at, Aulweg
129, D-35392 Giessen, Germany
APStracts 3:0217H, 1996.
The effect of neuropeptide Y (NPY) on cellular adenosine 3',5'-cyclic
monophosphate (cAMP) contents and macromolecule permeability was
studied in cultured monolayers of microvascular coronary endothelial
cells from rat. Macromolecule permeability was continuously
determined as passage of albumin across the monolayers. NPY (10-10 to
10-7 M) decreased albumin flux and cellular cAMP content in a dose
-dependent manner with half-maximal effect (EC50) on albumin flux at
1.4 x 10-9 M and on cAMP contents at 0.7 x 10-9 M. A maximum effect
of NPY was observed at 10-7 M, decreasing albumin flux by 71 + 8% and
cellular cAMP contents by 80 + 9% (mean+SD, n = 6, p<0.05)
compared to control. The effect of NPY on albumin flux was not
altered in presence of indomethacin (10-5 M; inhibitor of
cyclooxygenase) and NG-nitro-L-arginine (10-5 M; inhibitor of nitric
oxide synthase). NPY (10-7 M) also antagonized the increase of
albumin flux and cAMP content induced by isoproterenol (10-6 M).
Pretreatment of endothelial monolayers with pertussis toxin
(1?[mu]g/ml for 2 h) abolished the effect of NPY on albumin flux and
cAMP contents. This study shows that NPY can modulate macromolecule
permeability of endothelial monolayers by reducing the cellular cAMP
contents. Together with the effect of pertussis toxin the data
suggest that NPY exerts its antiadrenergic effect on cAMP metabolism
and endothelial barrier function by receptors linked to adenylyl
cyclase via an inhibitory guanosine-binding protein in coronary
endothelial cells.
Received 18 July 1995; accepted in final form 10 May 1996.
APS Manuscript Number H675-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 June 96