ATP and β, γ-methylene ATP produce relaxation of guinea-pig isolated trachealis muscle via actions at P1 purinoceptors

• Published in: European journal of pharmacology Vol. 307; no. 2; pp. 183 - 190
• Main Authors: PIPER, A. S, HOLLINGSWORTH, M
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 27.06.1996
• Subjects: Adenosine Triphosphate - analogs & derivatives; Adenosine Triphosphate - antagonists & inhibitors; Adenosine Triphosphate - pharmacology; Air breathing; Animals; Biological and medical sciences; Carbachol - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Guinea Pigs; In Vitro Techniques; Indomethacin - pharmacology; Male; Muscle Contraction - drug effects; Muscle Relaxation - drug effects; Parasympatholytics - pharmacology; Receptors, Purinergic P1 - drug effects; Receptors, Purinergic P1 - physiology; Receptors, Purinergic P2 - drug effects; Receptors, Purinergic P2 - physiology; Respiratory system: anatomy, metabolism, gas exchange, ventilatory mechanics, respiratory hemodynamics; Suramin - pharmacology; Theophylline - analogs & derivatives; Theophylline - pharmacology; Thioinosine - analogs & derivatives; Thioinosine - pharmacology; Trachea - drug effects; Vertebrates: respiratory system; Agonist; Bronchodilator; Rodentia; Contractility; Smooth muscle; In vitro; Biological activity; Relaxation; Vertebrata; Mammalia; Guinea pig; Analog; Neuromediator; Antagonist; Adenosine receptor; Mechanism of action; ATP; Trachea
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(96)00237-3

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.