Involvement of mast cells, sensory afferents and sympathetic mechanisms inpaw oedema induced by adenosine A(1) and A(2B/3) receptor agonists

Both the adenosine A(1) receptor agonist N-6-cyclopentyladenosine and the a denosine A(2B/3) receptor agonist N-6-benzyl-5'-N-ethylcarboxamido adenosin e (N-6-B-NECA) produce an acute paw oedema response following local s.c. in jection into the rat hindpaw. This study characterized aspects of the mecha nisms by which these responses occur by determining the effect of compound 48/80 (mast cell depleting agent), capsaicin (sensory neurotoxin) and 6-hyd roxydopamine (sympathetic nervous system neurotoxin) on the paw oedema resp onse produced by these agents. Compound 48/80 markedly reduced the increase in paw volume produced by both N-6-cyclopentyladenosine and N-6-B-NECA. Ca psaicin significantly reduced paw oedema induced by N-6-cyclopentyladenosin e but not N-6-B-NECA. In contrast, 6-hydroxydopamine reduced paw oedema ind uced by N-6-B-NECA but not N-6-cyclopentyladenosine. These results indicate an involvement of mast cells in paw oedema produced by both adenosine A(1) and A(2B/3) receptor agonists. For N-6-cyclopentyladenosine, this involvem ent may be a secondary involvement due to activation of a neurogenic mechan ism, but for N-6-B-NECA, it may be a direct effect on mast cells. The natur e of the involvement of the sympathetic nervous system in the action of N-6 -B-NECA is not entirely clear. (C) 2000 Elsevier Science B.V. All rights re served.