Involvement of mast cells, sensory afferents and sympathetic mechanisms in paw oedema induced by adenosine A₁ and A(2B/3) receptor agonists

Both the adenosine A₁ receptor agonist N⁶-cyclopentyladenosine and the adenosine A(2B/3) receptor agonist N⁶-benzyl-5'-N-ethylcarboxamido adenosine (N⁶-B-NECA) produce an acute paw oedema response following local s.c. injection into the rat hindpaw. This study characterized aspects of the mechanisms by which these responses occur by determining the effect of compound 48/80 (mast cell depleting agent), capsaicin (sensory neurotoxin) and 6-hydroxydopamine (sympathetic nervous system neurotoxin) on the paw oedema response produced by these agents. Compound 48/80 markedly reduced the increase in paw volume produced by both N⁶-cyclopentyladenosine and N⁶-B- NECA. Capsaicin significantly reduced paw oedema induced by N⁶- cyclopentyladenosine but not N⁶-B-NECA. In contrast, 6-hydroxydopamine reduced paw oedema induced by N⁶-B-NECA but not N⁶-cyclopentyladenosine. These results indicate an involvement of mast cells in paw oedema produced by both adenosine A₁ and A(2B/3) receptor agonists. For N⁶- cyclopentyladenosine, this involvement may be a secondary involvement due to activation of a neurogenic mechanism, but for N⁶-B-NECA, it may be a direct effect on mast cells. The nature of the involvement of the sympathetic nervous system in the action of N⁶-B-NECA is not entirely clear. (C) 2000 Elsevier Science B.V.