Erythrocyte adenosine transport: effects of Ca2+ channel antagonists and ions.
On the basis of observations of adenosine-Ca2+ competition, we assessed the effects on erythrocyte adenosine transport of Ca2+ channel antagonists, mono- and divalent cations, and Cl- and Cl- transport inhibitors. The Ca2+ channel antagonists, diltiazem and verapamil, competitively inhibited adenosine influx (Ki = 158 +/- 17.4 and 13.5 +/- 1.3 microM at 10 microM adenosine, respectively), despite no apparent effect on transport by Ca2+, Mg2+, Na+, or K+. Verapamil also inhibited uridine efflux (Ki = 1.7 +/- 0.3 microM at 84-100 microM intracellular uridine). The absence of Cl- decreased adenosine influx rates from 0.615 +/- 0.013 to 0.386 +/- 0.008 nmol X s-1 X ml intracellular H2O-1. The Cl- transport inhibitors, diisothiocyanostilbene disulfonate (10 microM), furosemide (1 mM), and NO-3 (145 mM), decreased adenosine influx rates to 0.301 +/- 0.008, 0.325 +/- 0.013, and 0.430 +/- 0.009 nmol X s-1 X ml intracellular H2O-1, respectively. These studies indicate that the Ca2+ channel antagonists inhibit adenosine release and uptake and therefore may modulate adenosine-mediated events. Additionally, they suggest that adenosine and anion transport systems are linked or share common features.
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000097:blood*; D000328:Adult; D001692:Biological Transport; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002412:Cations / Q000494:pharmacology*; D002712:Chlorides / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008274:Magnesium / Q000494:pharmacology; D014529:Uridine / Q000097:blood; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002412:Cations; D002712:Chlorides; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D014700:Verapamil; D004110:Diltiazem; D008274:Magnesium; D000241:Adenosine; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D014529:Uridine