title: Evidence that ATP acts at two sites to evoke contraction in the rat isolated tail artery.
abstract: 1. The site(s) at which P2-receptor agonists act to evoke contractions of the rat isolated tail artery was studied by use of P2-receptor antagonists and the extracellular ATPase inhibitor 6-N,N-diethyl-D-beta,gamma-dibromomethyleneATP (ARL 67156). 2. Suramin (1 microM(-1) mM) and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (0.3-300 microM) inhibited contractions evoked by equi-effective concentrations of alpha,beta-methyleneATP (alpha,beta-meATP) (5 microM), 2-methylthioATP (2-meSATP) (100 microM) and adenosine 5'-triphosphate (ATP) (1 mM) in a concentration-dependent manner. Responses to alpha,beta-meATP and 2-meSATP were abolished, but approximately one third of the peak response to ATP was resistant to suramin and PPADS. 3. Contractions evoked by uridine 5'-triphosphate (UTP) (1 mM) were slightly inhibited by suramin (100 and 300 microM) and potentiated by PPADS (300 microM). 4. Desensitization of the P2X1-receptor by alpha,beta-meATP abolished contractions evoked by 2-meSATP (100 microM) and reduced those to ATP (1 mM) and UTP (1 mM) to 15+/-3% and 68+/-4% of control. 5. Responses to alpha,beta-meATP (5 microM) and 2-meSATP (100 microM) were abolished when tissues were bathed in nominally calcium-free solution, while the peak contractions to ATP (1 mM) and UTP (1 mM) were reduced to 24+/-6% and 61+/-13%, respectively, of their control response. 6. ARL 67156 (3-100 microM) potentiated contractions elicited by UTP (1 mM), but inhibited responses to alpha,beta-meATP (5 microM), 2-meSATP (100 microM) and ATP (1 mM) in a concentration-dependent manner. 7. These results suggest that two populations of P2-receptors are present in the rat tail artery; ligand-gated P2X1-receptors and G-protein-coupled P2Y-receptors.
authors.affiliation: Department of Physiology and Pharmacology, University of Strathclyde, Glasgow.
authors.forename: G J
authors.initials: GJ
authors.lastname: McLaren
authors.forename: K S
authors.initials: KS
authors.lastname: Burke
authors.forename: K J
authors.initials: KJ
authors.lastname: Buchanan
authors.forename: P
authors.initials: P
authors.lastname: Sneddon
authors.forename: C
authors.initials: C
authors.lastname: Kennedy
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011983:Receptors, Purinergic / Q000145:classification / Q000187:drug effects / Q000502:physiology; D013498:Suramin / Q000494:pharmacology; D013623:Tail / Q000098:blood supply
chemical_list: C092431:6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP; D004791:Enzyme Inhibitors; D011983:Receptors, Purinergic; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D013498:Suramin; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C002630:alpha,beta-methyleneadenosine 5'-triphosphate