Adenosine potentiates immunological histamine release from rat mast cells by a novel cyclic AMP‐independent cell‐surface action

Abstract

Adenosine enhanced histamine release and prolonged the adenosine 3': '-cyclic monophosphate (cyclic AMP) response in purified rat peritoneal mast cells following immunological challenge. The effect on the cyclic AMP response, which was blocked by 8-phenyltheophylline, probably results from an interaction with A2-purinoceptors. Enhancement of histamine release showed different characteristics. It was not inhibited by dipyridamole or hexobendine, thereby indicating an action at the cell surface. However, the relative potencies of adenosine analogues and nucleotides, together with the observation that this effect was not antagonized by 8-phenyltheophylline or theophylline, suggest that it is not mediated by a previously recognised purinoceptor. Thus, enhancement of histamine release may represent a novel cell surface action of adenosine which is independent of its effects on adenylate cyclase.

Identification of A3 Receptor- and Mast Cell-Dependent and -Independent Components of Adenosine-Mediated Airway Responsiveness in Mice

“…These findings are also consistent with human studies showing adenosine-induced histamine release from bronchoalveolar lavage mast cells (39). However, these observations do contrast with those of some other studies (2,30,40,41), including one of our own studies in which we showed that while adenosine, acting via the A 3 receptor, could enhance the degranulation of bone marrow mast cells in response to IgE and specific Ag, adenosine alone was ineffective at mediating bone marrow mast cell degranulation (30). However, in this issue Zhong et al (42) demonstrate that adenosine can induce degranulation of mast cells that have been derived in vitro from mouse pulmonary mast cells, a result consistent with the findings in our in vivo studies of mouse airway mast cells in situ.…”

Studies on the receptor mediating cyclic AMP‐independent enhancement by adenosine of IgE‐dependent mediator release from rat mast cells

“…Adenosine enhances IgE-dependent mediator release from rat serosal mast cells (Marquardt et al, 1978;Holgate et al, 1980;Burt & Stanworth, 1983;Nishibori et al, 1983;Church & Hughes, 1985;Vardey & Skidmore, 1985). This effect has been suggested to result from the interaction of adenosine with cell surface A2-purinoceptors to activate adenylate cyclase (Van Calker et al, 1979;Londos et al, 1980).…”

Inosine binds to A3 adenosine receptors and stimulates mast cell degranulation.

“…200 l of the supernatants were removed and added to 50 l 5 mM p-nitrophenyl-N-acetyl-d-glucosaminide, 100 mM citric acid, pH 3.8, and incubated at 37ЊC for 2 h with shaking to measure ␤-hexosaminidase activity. The reactions were stopped by addition of 50 l of 0.4 M NaCO 3 . To measure total ␤-hexosaminidase content, 50 l of lysis buffer (complete Tyrode's buffer plus 0.6% Triton X-100) was added to 250-l aliquots of cells, and 20 l was removed and analyzed.…”

“…Before this discovery, Church and Hughes (3) had noted that adenosine facilitates immunological stimulation of histamine release from rat peritoneal mast cells that is not blocked by xanthines (known to block A 1 and A 2 adenosine receptors), suggesting that facilitation of histamine release is mediated by a then unrecognized purinoceptor. It is now known that insensitivity to xanthine blockade is a characteristic of rat, but not human, A 3 adenosine receptors (4,5).…”