The effects of adenosine and its analogues on cAMP-responses and histamine release of rat peritoneal mast cells were investigated. The adenosine analogue 5'-N-ethylcarboxamidoadenosine (NECA') activates the adenylate cyclase of the mast cell membranes and elevates the cAMP-levels of the intact mast cells. Both effects are antagonized by methylxanthines, suggesting that they are mediated via an A2 adenosine receptor. Adenosine and its analogues enhance the release of histamine from these cells, when the release is stimulated either by the calcium ionophore A 23187 or by concanavalin A. However, this effect is not antagonized by theophylline or 8-phenyltheophylline. In contrast, it is antagonized by the adenosine uptake blockers S-(p-nitrobenzyl)-6-thioinosine (NBTI) and S-(p-nitrobenzyl)-6-thioguanosine (NBTG). It is concluded that adenosine has two different effects on mast cells: it activates adenylate cyclase via an A2 adenosine receptor, and it enhances histamine release via an action at an intracellular site.
Introduct1onStimulation of mast cells with appropriate antigen results in the rapid release of a large number of mediators of allergy from the cells.The cells possess cell surfa~e receptors for the Fe portion of IgE which serve to transmlt the signal of binding of an antigen by the lgE molecule to the interior of the cell.Since Studies of mast cells are complicated by important intraand inter-species differences. With1n a species~ there appear to be at least two groups of mast cells (review~d bY Enerback 1986).The first group i s the connective t1ssu~ mast cells, which is the most frequently studied type ~ mast cell s and i ncl udes, for exampl e the mast cel s obta i ned by peri tonea 1 1 avage.The seco~d group represents the ~ucosal mast cell s, which differ histologically, funct1onally and in their response to pharmacological agents from those of the first group. Blood basophils are, lik~ m~st cel_l s, der~ ved from bone marrow precursors, but. thei flnal d1fferent1ation in the blood rather than in t1ss~e~ ap~ears to result in yet another spectrum of propertleh ( ~ 1 tamura et a 1. 1983).Th i s heterogene 1 ty tagether wi t d1fferences b~tween species, and often between strains. 0~
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