Polymorphonuclear leukocyte motility in vitro. VI. Effect of purine and pyrimidine analogues: possible role of cyclic AMP.

Abstract

Abstract The effect of several purine and pyrimidine analogues (5 × 10 −4 M) on random PMN (polymorphonuclear leukocyte) motility in vitro was studied, using a modification of the Boyden Chamber technique. The purines, xanthine, hypoxanthine, adenine, and guanine stimulated random PMN motility to about the same extent as uric acid, whereas the dimethyl xanthines, theobromine, and theophylline, were much less effective and the trimethyl xanthine, caffeine, actually inhibited motility. The pyrimidines, uracil and 1, 3-dimethyl uracil, had no effect on PMN motility but 5-methyl uracil (thymine) was found to be as potent as uric acid in stimulating motility suggesting that a substituent at position-5 of the pyrimidine nucleus is probably essential for this latter function. Exposure of leukocytes to cyclic 3′,5′ AMP (adenosine monophosphate) (cAMP) resulted in a dose-related inhibition of both random and directed PMN motility. Various substances known to alter intracellular cAMP levels were found to affect PMN motility. Those agents reported by others to increase intracellular cAMP in other tissues, particularly in platelets, retarded motility whereas those reported to decrease intracellular cAMP levels augmented PMN motility in the present studies.