title: ATP and beta,gamma-methylene ATP produce relaxation of guinea-pig isolated trachealis muscle via actions at P1 purinoceptors.
abstract: 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.
authors.affiliation: Smooth Muscle Pharmacology Group, School of Biological Sciences, University of Manchester, UK.
authors.forename: A S
authors.initials: AS
authors.lastname: Piper
authors.forename: M
authors.initials: M
authors.lastname: Hollingsworth
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology*; D018047:Receptors, Purinergic P1 / Q000187:drug effects* / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology; D013498:Suramin / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
chemical_list: D010276:Parasympatholytics; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; D013868:Thioinosine; D013498:Suramin; C031433:8-(4-sulfophenyl)theophylline; D000255:Adenosine Triphosphate; D002217:Carbachol; D013806:Theophylline; C001789:4-nitrobenzylthioinosine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D007213:Indomethacin