Acute paw oedema induced by local injection of adenosine A₁, A₂ and A₃ receptor agonists

The present study used plethysmometry to examine oedema following local injection of selective adenosine A₁, A₂ and A₃ receptor agonists and inhibitors of adenosine metabolism into the hindpaw of the rat. N⁶- Cyclopentyladenosine and L-N⁶-phenylisopropyladenosine (A₁), 2-[p(2- carboxyethyl) phenethylamino]-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS21680) (A(2A)) and N⁶-benzyl-5'-N-ethylcarboxamido adenosine (N⁶-B- NECA) (A₃) all produced an increase in paw volume (N⁶-B-NECA > N⁶- cyclopentyladenosine, L-N⁶-phenylisopropyladenosine > CGS21680). At the highest dose, each agent also produced a systemically mediated suppression of oedema. Oedema by N⁶-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 N⁶-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 N⁶-cyclopentyladenosine and N⁶-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 A₁, A₂ and A₃ receptor agonists, which likely results from different mechanisms of action in each case.