Functional antagonism between camp and cgmp on macromolecule
permeability of coronary endothelial monolayers.
Hempel, A., T. Noll, A. Muhs, H. M. Piper.
Physiologisches Institut, Justus-Liebig-Universit[umlaut]at, Aulweg
129, D-35392 Giessen, Germany
APStracts 2:0411H, 1995.
The role of the intracellular second messenger guanosine 3',5'-cyclic
monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP)
for the control of macromolecule permeability was studied in cultured
monolayers of microvascular coronary endothelial cells from rat.
Macromolecule permeability was determined as passage of fluorescein
isothiocyanate (FITC) -labeled albumin across the monolayers.
Activation of adenylyl cyclase by the [beta]-adrenoceptor agonist
isoproterenol (10-5?M), and the A2-adenosine receptor agonist 5'-(N
-ethylcarboxamido)adenosine (10-7?M; NECA) induced an increase in
cellular cAMP contents which was accompanied by an increase in
albumin flux. Effects of isoproterenol and NECA on cellular cAMP
level and albumin flux could be antagonized by a stimulator of the
particulate guanylyl cyclase, atrial natriuretic peptide (10-7?M;
ANP), and stimulators of the soluble guanylyl cyclase, 3
-morpholinosydnonimine (10-7?M, SIN-1) and sodium nitroprusside (10
-6?M; SNP). ANP, SIN-1, and SNP also reduced cAMP content and basal
macromolecule flux in unstimulated monolayers. 8-bromo-cGMP (5 x 10-6
M; 8-Br-cGMP), a stimulator of protein kinase G, reduced the increase
in albumin flux under isoproterenol (10-5 M), NECA (10-7 M) or 8
-bromo-cAMP (5 x 10-6 M, 8-Br-cAMP). The present study shows that cGMP
and cAMP are functional antagonists in the control of macromolecule
permeability.
Received 6 March 1995; accepted in final form 7 September 1995.
APS Manuscript Number H210-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.