thioinosine and 5--adenylyl-(beta-gamma-methylene)diphosphonate

Adenosine 5'-triphosphate (ATP), beta, gamma-methylene ATP and alpha, beta-methylene ATP produced relaxation of carbachol-precontracted isolated trachealis muscle from the guinea-pig in the presence of indomethacin (2.8 microM) and the adenosine uptake inhibitor S-(4-nitrobenzyl)-6-thioinosine (NBTI; 300 nM). The potency order for ATP and analogues was: beta, gamma-methylene ATP = ATP > alpha, beta-methylene ATP = uridine 5'-triphosphate (UTP) = 2-methylthio ATP. Adenosine and 5'-N-ethylcarboxamidoadenosine (NECA) also caused relaxation. Relaxations to ATP, beta, gamma-methylene ATP, adenosine and NECA were not inhibited by the P2 purinoceptor antagonist suramin (100 microM), but were inhibited by the P1 purinoceptor antagonist 8-sulphophenyltheophylline (140 microM). NBTI significantly potentiated adenosine and ATP but not beta, gamma-methylene ATP or NECA. The data are compatible with the idea that beta, gamma-methylene ATP could interact directly with P1 purinoceptors while ATP acts indirectly at P1 purinoceptors via conversion to adenosine.

Topics: Adenosine Triphosphate; Animals; Carbachol; Female; Guinea Pigs; In Vitro Techniques; Indomethacin; Male; Muscle Contraction; Muscle Relaxation; Parasympatholytics; Receptors, Purinergic P1; Receptors, Purinergic P2; Suramin; Theophylline; Thioinosine; Trachea

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Biological Transport, Active; Carrier Proteins; Cytochalasin B; Deoxyguanosine; Deoxyribonucleosides; Guanosine; Inosine; Intracellular Membranes; Kinetics; Membrane Proteins; Mitochondria, Liver; Rats; Thioinosine; Thionucleosides