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.
Ziganshina
L E
LE
Department of Anatomy and Developmental Biology, University College London, UK.
Ziganshin
A U
AU
Hoyle
C H
CH
Burnstock
G
G
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