PGBX, a prostagandin derivative, mimics the action of the calcium ionophore A23187 on human neutrophils.
The interactions have been studied of a water-soluble, polymeric derivative of prostaglandin B1, PGBX, with human polymorphonuclear leukocytes (PMN). PGBX, which is a potent ionophore of divalent cations, provoked superoxide anion (O2.-) generation and lysosomal enzyme release in cytochalasin B-treated PMN in the presence of extracellular divalent cations (Ca2+, Sr2+, Mg2+, Mn2+, Ba2+). Kinetic and dose-response studies showed that PGBX mimicked te action of ionophore A23187 in PMN. Both ionophores induced superoxide generation and release of enzymes from specific and azurophil granules (lysozyme > beta-glucuronidase) without provoking release of the cytoplasmic marker enzyme lactic dehydrogenase. In contrast, the precursor of PGBX, prostaglandin B1 (PGB1), and arachidonate did not mimic ionophore-induced stimulation of PMN. PGBX induced enzyme release both in the presence of extracellular Ca2+ and Ba2+ (both of which it translocates in model liposomes), whereas A23187 showed specificity for Ca2+ (which it translocates preferentially over Ba2+). These studies indicate that the actions of a water-soluble polymer (PGBX) derived from a naturally occurring prostaglandin (PGB1) on human neutrophils resemble those of a classical ionophore (A23187). Moreover, they provide additional evidence that increments in the intracellular levels of divalent cations may signal stimulus-secretion coupling in human neutrophils.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent; D003571:Cytochalasin B / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008247:Lysosomes / Q000201:enzymology; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D011453:Prostaglandins / Q000494:pharmacology*; D011456:Prostaglandins B / Q000494:pharmacology*; D013481:Superoxides / Q000096:biosynthesis
D000900:Anti-Bacterial Agents; D002413:Cations, Divalent; D011453:Prostaglandins; D011456:Prostaglandins B; D013481:Superoxides; D000001:Calcimycin; D003571:Cytochalasin B; D002118:Calcium