Preglomerular microcirculation expresses the cAMP-adenosine pathway.
The purpose of this study was to investigate whether the extracellular cAMP-adenosine pathway (i.e., transport of cAMP out of cells followed by extracellular conversion of cAMP to adenosine) exists in preglomerular microvessels (PGMVs). Incubation of PGMVs for 1 h with 30 microM cAMP increased the amount of extracellular adenosine from 163 +/- 18.6 (n = 18) to 9810 +/- 604 (n = 12) pmol/mg of protein (P < 10(-6)). The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX; 1 mM; n = 6) and the ecto-phosphodiesterase inhibitor 1, 3-dipropyl-8-p-sulfophenylxanthine (DPSPX; 1 mM; n = 6) significantly (P < 10(-6) and P < 10(-5), respectively) reduced the cAMP-induced increase in extracellular adenosine. Incubation of PGMVs for 1 h with isoproterenol (beta-adrenoceptor agonist; 1 microM) + IBMX (0.1 mM) increased the amount of extracellular cAMP from 0.800 +/- 0.047 to 22.3 +/- 2.20 pmol/mg of protein (P < 10(-6); n = 41). In PGMVs incubated with isoproterenol (1 microM) + IBMX (0.1 mM) for 1 h, there was a significant (P < 10(-4)) linear (r(2) = 0.6) relationship between intracellular and extracellular cAMP levels. Incubation of PGMVs for 1 h with 1 microM isoproterenol increased the amount of extracellular adenosine from 163 +/- 18.6 (n = 18) to 297 +/- 38.3 (n = 12) pmol/mg of protein (P =.002). Propranolol (beta-adrenoceptor antagonist; 1 microM; n = 7), IBMX (1 mM; n = 14), and DPSPX (1 mM; n = 12) blocked (P =.037, P =.015, and P =.026, respectively) isoproterenol-induced increases in extracellular adenosine.


CONCLUSIONS
PGMVs transport endogenous cAMP to the extracellular compartment and metabolize extracellular cAMP to adenosine. This pathway can increase extracellular levels of adenosine during beta-adrenoceptor activation of adenylyl cyclase.
Jackson
E K
EK
Center for Clinical Pharmacology, Departments of Pharmacology and Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. edj+@pitt.edu
Mi
Z
Z
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000241:Adenosine / Q000096:biosynthesis*; D000262:Adenylyl Cyclases / Q000502:physiology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000378:metabolism; D051381:Rats; D014970:Xanthines / Q000494:pharmacology
D014970:Xanthines; C053896:1,3-dipropyl-8-(4-sulfophenyl)xanthine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000241:Adenosine; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine