Acute paw oedema induced by local injection of adenosine A(1), A(2) and A(3) receptor agonists.
The present study used plethysmometry to examine oedema following local injection of selective adenosine A(1), A(2) and A(3) receptor agonists and inhibitors of adenosine metabolism into the hindpaw of the rat. N(6)-Cyclopentyladenosine and L-N(6)-phenylisopropyladenosine (A(1)), 2-[p(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS21680) (A(2A)) and N(6)-benzyl-5'-N-ethylcarboxamido adenosine (N(6)-B-NECA) (A(3)) all produced an increase in paw volume (N(6)N(6)-cyclopentyladenosine, L-N(6)CGS21680). At the highest dose, each agent also produced a systemically mediated suppression of oedema. Oedema by N(6)-cyclopentyladenosine was blocked by caffeine, 8-cyclopentyl-1,3-dimethylxanthine and enprofylline. Oedema by CGS21680 was blocked by caffeine and 8-cyclopentyl-1, 3-dimethylxanthine. Oedema by N(6)-B-NECA was blocked by enprofylline, but not by caffeine or 8-cyclopentyl-1, 3-dimethylxanthine, or by systemic administration of MRS 1191. Oedema by both N(6)-cyclopentyladenosine and N(6)-B-NECA was blocked by mepyramine, ketanserin and phentolamine, but that by CGS21680 was not. The adenosine kinase inhibitor 5'-amino-5'-deoxyadenosine and the adenosine deaminase inhibitor 2'-deoxycoformycin produced only a limited increase in paw volume, and this was blocked by caffeine. This study demonstrates an acute paw oedema response following local administration of adenosine A(1), A(2) and A(3) receptor agonists, which likely results from different mechanisms of action in each case.
Sawynok
J
J
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada. sawydalu@is.dal.ca
Reid
A
A
Liu
X J
XJ
D000208:Acute Disease; D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology; D058892:Adenosine Deaminase Inhibitors; D000248:Adenosine Kinase / Q000037:antagonists & inhibitors; D000818:Animals; D002110:Caffeine / Q000009:adverse effects / Q000494:pharmacology; D004347:Drug Interactions; D004487:Edema / Q000139:chemically induced*; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000009:adverse effects / Q000494:pharmacology; D008297:Male; D010627:Phenethylamines / Q000009:adverse effects / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D011738:Pyrilamine / Q000009:adverse effects / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043684:Receptor, Adenosine A3
D058892:Adenosine Deaminase Inhibitors; D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043684:Receptor, Adenosine A3; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C084956:N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine; D002110:Caffeine; D000248:Adenosine Kinase; D011738:Pyrilamine; D000241:Adenosine