A2-adenosine receptor stimulation increases macromolecule permeability of coronary endothelial cells.
The effect of the A2-adenosine receptor agonist 5'-(N-ethylcarboxamido)adenosine (NECA) on macromolecule permeability (PM; indicator fluorescein isothiocyanate-labeled albumin) of endothelial cells was investigated using confluent monolayers of rat coronary microvascular endothelial cells (CEC) and porcine aortic macrovascular endothelial cells (AEC). In CEC, NECA (10(-7) M) increased PM by 39%. Similar results were obtained by isoproterenol (10(-6) M) and forskolin (10(-5) M). The effect of NECA could be antagonized by 8-phenyltheophylline (8-PT; 10(-5) M). In AEC, NECA (10(-7) M) caused an opposite effect in that it decreased PM by 26% as did isoproterenol (10(-6) M) and forskolin (10(-5) M). The response to NECA was abolished in the presence of 8-PT (10(-5) M). In AEC but not CEC, NECA could reduce the rise in PM caused by endothelial energy depletion (in the presence of 5 mM KCN and 5 mM 2-deoxy-D-glucose). It was common to AEC and CEC that NECA (10(-7) M), isoproterenol (10(-6) M), and forskolin (10(-5) M) stimulated production of adenosine 3',5'-cyclic monophosphate (cAMP). The stimulatory effect of NECA on production of cAMP could be antagonized by 8-PT (10(-5) M). In summary, the results indicate that in AEC and CEC PM is modulated by an A2-adenosine receptor-mediated stimulation of adenylate cyclase. The secondary effects of stimulation of adenylate cyclase are different in CEC and AEC, however, since it caused a reduction of PM in AEC, but an increase in CEC.
Watanabe
H
H
Physiologisches Institut I, Universität Düsseldorf, Federal Republic of Germany.
Kuhne
W
W
Schwartz
P
P
Piper
H M
HM
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D002199:Capillary Permeability; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003331:Coronary Vessels / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D000242:Cyclic AMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D004734:Energy Metabolism; D007545:Isoproterenol / Q000494:pharmacology; D046911:Macromolecular Substances; D008855:Microscopy, Electron, Scanning; D011983:Receptors, Purinergic / Q000502:physiology*
D046911:Macromolecular Substances; D011983:Receptors, Purinergic; D005576:Colforsin; D019830:Adenosine-5'-(N-ethylcarboxamide); D000242:Cyclic AMP; D000241:Adenosine; D007545:Isoproterenol