title: Adenosine uptake sites in dog heart and brain; interaction with calcium antagonists.
abstract: [3H] Nitrobenzylthioinosine (NBI) binding is characterized in dog heart and brain. Evidence is presented suggesting that [3H]NBI is binding to the adenosine uptake site in both tissues. Physiologic studies in open-chested dogs clearly demonstrate that NBI acts as a coronary vasodilator, consistent with an action at the adenosine uptake site. The binding is reversible, saturable and of high affinity (KD = 0.78 +/- .06 nM for heart and 0.52 +/- .05 nM for brain). Both dipyridamole and hexobendine are high potency inhibitors of [3H]NBI binding in heart and brain while other antihypertensives and vasodilators such as propranolol and nitroglycerin have no effect. The inhibition of [3H]NBI binding observed with dipyridamole was competitive indicating that both agents are acting at the same site. The dihydropyridine calcium antagonists also inhibited binding with a lower potency than the adenosine uptake blockers. Non-dihydropyridine calcium antagonists were much less potent in this regard. The inhibition of [3H]NBI binding observed with the dihydropyridine calcium antagonists was non-competitive suggesting that the calcium channel and adenosine uptake site may be coupled to each other.
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism*; D003326:Coronary Circulation / Q000187:drug effects; D004176:Dipyridamole / Q000494:pharmacology; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D007288:Inosine / Q000031:analogs & derivatives*; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D013868:Thioinosine; D007288:Inosine; D004176:Dipyridamole; C001789:4-nitrobenzylthioinosine; D000241:Adenosine