The role of cyclic AMP in the chemotactic responsiveness and spontaneous motility of rabbit peritoneal neutrophils. The inhibition of neutrophil movement and the elevation of cyclic AMP levels by catecholamines, prostaglandins, theophylline and cholera toxin.
Agents known to affect intracellular levels of cyclic AMP in many diverse systems have been tested for their effect on the chemotaxis induced by Escherichia coli culture filtrates, spontaneous motility and cyclic AMP levels of rabbit peritoneal neutrophils. Prostaglandin E1 and A1 but not prostaglandin F2alpha increased neutrophil cyclic AMP levels and, correspondingly, only the former two prostaglandins inhibited chemotaxis. Nevertheless, a quantitative relationship between prostaglandin stimulation of cyclic AMP and inhibition of chemotaxis could not be found. Epinephrine, isoproterenol, and, to a much lesser extent, norepinephrine increased neutrophil cyclic AMP through beta adrenergic stimulation. Only epinephrine and isoproterenol inhibited chemotaxis, but the inhibition was variable and not related to the ability of these catecholamines to increase intracellular cyclic AMP. Cholera toxin increased neutrophil cyclic AMP after a 30-min lag period which paralled its inhibitory effect on chemotaxis and spontaneous motility. However, the effect on chemotaxis require 50 ng/ml of toxin whereas the effect on cyclic AMP was manifested at 2 ng/ml of toxin. Prior to 30-min preincubation there was no effect of even 1250 ng/ml of toxin on either cyclic AMP or chemotaxis. Choleragenoid prevented the effects of toxin on both cyclic AMP and chemotaxis. The bacterial chemotactic factor obtained from E. coli culture filtrates did not effect a measurable change in levels of neutrophil cyclic AMP. The data indicate that even though cyclic AMP is not, in the main sequence of events, triggering the chemotactic response, increases in neutrophil cyclic AMP may modulate the movement and thus the chemotactic responsiveness of the neutrophil.
D000818:Animals; D001202:Ascitic Fluid / Q000276:immunology; D002395:Catecholamines / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects*; D002633:Chemotaxis / Q000187:drug effects*; D002771:Cholera / Q000276:immunology; D000242:Cyclic AMP / Q000032:analysis / Q000276:immunology*; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D009504:Neutrophils / Q000032:analysis / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology; D011817:Rabbits; D011863:Radioimmunoassay; D013806:Theophylline / Q000494:pharmacology; D013997:Time Factors; D014118:Toxins, Biological / Q000494:pharmacology
D002395:Catecholamines; D011453:Prostaglandins; D014118:Toxins, Biological; D011433:Propranolol; D013806:Theophylline; D000242:Cyclic AMP; D007545:Isoproterenol; D004837:Epinephrine