title: Adenosine inhibits immunoglobulin E-dependent histamine secretion from human basophil leukocytes by two independent mechanisms.
abstract: Adenosine inhibits immunoglobulin E-dependent histamine release when preincubated with human basophil leukocytes before challenge. Two distinct mechanisms for this inhibition have been demonstrated. The first we suggest to be an A2-purinoceptor mediated mechanism. This effect, which is apparent with both 15- and 60-min preincubation periods, is mimicked by 5'-N-ethylcarboxamideadenosine, blocked by 8-phenyltheophylline but not dipyridamole and is associated with the ability of adenosine to elevate cyclic AMP. The second, which is mimicked by 3-deazaadenosine and is associated only with the longer 60-min preincubation period, is reversed by dipyridamole but not by 8-phenyltheophylline suggesting it to be an intracellular mechanism. Its enhancement by homocysteine thiolactone and reversal by exogenous S-adenosyl methionine suggests it to result from increasing intracellular S-adenosyl homocysteine levels. Our failure to detect increased 3H-methyl incorporation into chloroform-methanol extractable lipids after immunoglobulin E-dependent activation would indicate that inhibition of S-adenosyl methionine methylation reactions are an unlikely mechanism. As both prior stimulation of A2-purinoceptors and elevation of intracellular S-adenosyl homocysteine enhance and prolong the cyclic AMP response consequent upon immunoglobulin E-dependent activation, this represents a common mechanism by which histamine release may be suppressed.
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D001491:Basophils / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000032:analysis; D004176:Dipyridamole / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D008745:Methylation; D010743:Phospholipids / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014372:Tubercidin / Q000494:pharmacology
chemical_list: D010743:Phospholipids; C018258:3-deazaadenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D007073:Immunoglobulin E; D004176:Dipyridamole; D012436:S-Adenosylmethionine; D013806:Theophylline; D000242:Cyclic AMP; C028322:8-phenyltheophylline; D000241:Adenosine; D014372:Tubercidin