Adenosine A2 receptors reverse ischemia-reperfusion lung injury independent of beta-receptors.

Abstract

To evaluate the adenosine systems ability to reverse the endothelial damage produced by ischemia and reperfusion (I/R), we studied several different selective adenosine-receptor agonists and antagonists, a protein kinase A inhibitor, and a beta-adrenoreceptor antagonist in isolated buffer-perfused rat lungs. I/R (45 min/105 min) produced a sixfold increase in endothelial permeability as measured by the capillary filtration coefficient. Both a selective A2-receptor agonist (CGS-21680, 300 nM) and a beta-receptor agonist (isoproterenol, 10 microM) reversed the increased microvascular permeability. A nonselective adenosine-receptor antagonist (SPT, 20 microM) and a selective A1-receptor antagonist (DPCPX, 10 nM) had no effect on increased microvascular permeability. Also, isoproterenol and CGS-21680 reversed the damage being introduced after a selective A1-receptor agonist (CCPA, 100 nM). The nonspecific adenosine A1- and A2-receptor agonist NECA (12 nM) appeared to desensitize the A2 receptors and a protein kinase A inhibitor, adenosine-3',5'-cyclic monophosphothioate (Rp-cAMPS, 100 microM), blocked the reversal of endothelial damage by isoproterenol or A2-receptor agonist. Propranolol (100 microM) blocked the effect of isoproterenol but not the effect of CGS-21680. From this study we conclude that A2-receptor activation reverses endothelial damage associated with I/R by a mechanism independent of beta-receptors or Gi protein. However, a protein kinase A-3',5',-cyclic adenosine monophosphate pathway is activated by both the adenosine systems and beta-receptor activation.

• Authors: P L Khimenko, T M Moore, L W Hill, P S Wilson, S Coleman, A Rizzo, A E Taylor
• Journal: Journal of applied physiology (Bethesda, Md. : 1985) (J Appl Physiol (1985)) Vol. 78 Issue 3 Pg. 990-6 (Mar 1995) ISSN: 8750-7587 [Print] United States
• PMID: 7775345 (Publication Type: Journal Article)

Chemical References

• Receptors, Adrenergic, beta
• Receptors, Purinergic P1
• Adenosine-5'-(N-ethylcarboxamide)
• Cyclic AMP-Dependent Protein Kinases
• Adenosine

Topics

• Adenosine (analogs & derivatives, pharmacology)
• Adenosine-5'-(N-ethylcarboxamide)
• Animals
• Cyclic AMP-Dependent Protein Kinases (antagonists & inhibitors)
• Endothelium (pathology, physiopathology)
• Ischemia (pathology, physiopathology)
• Lung (pathology)
• Male
• Organ Size
• Pulmonary Circulation
• Rats
• Receptors, Adrenergic, beta (physiology)
• Receptors, Purinergic P1 (drug effects, physiology)
• Reperfusion Injury (pathology, physiopathology)