RT Journal Article
SR Electronic
T1 Preglomerular Microcirculation Expresses the cAMP-Adenosine Pathway
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 23
OP 28
VO 295
IS 1
A1 Jackson, Edwin K.
A1 Mi, Zaichuan
YR 2000
UL http://jpet.aspetjournals.org/content/295/1/23.abstract
AB 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 μM 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 (β-adrenoceptor agonist; 1 μM) + 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 μM) + IBMX (0.1 mM) for 1 h, there was a significant (P < 10−4) linear (r2 = 0.6) relationship between intracellular and extracellular cAMP levels. Incubation of PGMVs for 1 h with 1 μM 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 (β-adrenoceptor antagonist; 1 μM; 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 β-adrenoceptor activation of adenylyl cyclase. The American Society for Pharmacology and Experimental Therapeutics