Acute paw oedema formation induced by ATP: re-evaluation of the mechanisms involved.
ATP-induced inflammation was investigated using subplantar injection in the mouse hind paw. The order of efficacy of purinoceptor agonists for inducing paw oedema (30 nmol per paw) was ATP = alpha, beta-methylene ATP = 2-methylthio ATP > adenosine > UTP > ADP > AMP. Diadenosine polyphosphates effectively induced paw oedema formation with an order of efficacy of: P1,P4-di(adenosine-5')tetraphosphate = P1,P5-di(adenosine-5')-pentaphosphate = P1,P6-di(adenosine-5')hexaphosphate >>ATP = P1,P3-di(adenosine-5')triphosphate > P1,P2-di(adenosine-5')pyrophosphate. Systemic administration of P2-purinoceptor antagonists (30-100 mu mol/kg), suramin, 4,4'-diisothiocyanatostilbene-2,2'-disulphonate, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid and cibacron blue, reduced the intensity of ATP-induced oedema. At 30 mu mol/kg 8-(p-sulfophenyl)theophylline (non-selective adenosine receptor antagonist), 3,7-dimethyl-1,1-propargylxanthine (adenosine A2 receptor antagonist), triprolidine (histamine H1 receptor antagonist), ranitidine (histamine H2 receptor antagonist) and ketanserin (5-hydroxytryptamine 5-HT2 receptor antagonist), but neither 8-cyclopentyl-1,3-dipropylxanthine (adenosine A1 receptor antagonist), nor indomethacin (cyclooxygenase inhibitor) inhibited the ATP-induced swelling. Topical (100 nmol per paw), but not systemic (100 mu mol/kg) administration of NG-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor) reduced the intensity of the ATP-induced paw oedema. These results show that ATP can induce an inflammatory oedematous reaction and contribute to our understanding of the underlying mechanisms.
Department of Anatomy and Developmental Biology, University College London, UK.
L E
LE
Ziganshina
A U
AU
Ziganshin
C H
CH
Hoyle
G
G
Burnstock
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced; D006632:Histamine / Q000502:physiology; D007249:Inflammation / Q000139:chemically induced*; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018047:Receptors, Purinergic P1 / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000502:physiology; D012701:Serotonin / Q000502:physiology; D013498:Suramin / Q000494:pharmacology
D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D012701:Serotonin; D013498:Suramin; D006632:Histamine; D000255:Adenosine Triphosphate; D019331:NG-Nitroarginine Methyl Ester