n(6)-cyclopentyladenosine and Edema

Both the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine and the adenosine A(2B/3) receptor agonist N(6)-benzyl-5'-N-ethylcarboxamido adenosine (N(6)-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 N(6)-cyclopentyladenosine and N(6)-B-NECA. Capsaicin significantly reduced paw oedema induced by N(6)-cyclopentyladenosine but not N(6)-B-NECA. In contrast, 6-hydroxydopamine reduced paw oedema induced 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 involvement may be a secondary involvement due to activation of a neurogenic mechanism, but for N(6)-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 N(6)-B-NECA is not entirely clear.

Topics: Adenosine; Animals; Capsaicin; Dose-Response Relationship, Drug; Edema; Hindlimb; Male; Mast Cells; Neurons, Afferent; Oxidopamine; p-Methoxy-N-methylphenethylamine; Purinergic P1 Receptor Agonists; Rats; Rats, Sprague-Dawley; Receptor, Adenosine A2B; Receptor, Adenosine A3; Sympathetic Nervous System; Sympatholytics