Effect of the Ca2+ antagonist nifedipine on the release of platelet-activating factor (PAF-acether), slow-reacting substance and beta-glucuronidase from human neutrophils.
Ca2+ antagonists such as nifedipine (Nif) inhibit processes that depend on extracellular Ca2+ in many muscular and secretory cells. The effect of Nif on mediator release and Ca2+ uptake by human polymorphonuclear neutrophils (PMN) has been investigated. Nif caused a concentration-dependent inhibition of the Ca2+ ionophore-induced release of platelet-activating factor (PAF-acether), slow-reacting substance (SRS) and to a lesser degree beta-glucuronidase (beta-glu). Nif inhibited the synthesis of PAF-acether rather than its release. Increasing Ca2+ concentration in the bathing medium from 1.3 to 2.8 mM completely reversed the effect of Nif on PAF-acether secretion. Nif at 1 and 5 microM reduced PMN45Ca2+ uptake induced by the Ca2+ ionophore A 23187. These results indicate that the inhibition by Nif of mediator release depends probably on the Ca2+-antagonistic property of the drug. A preliminary ex vivo study suggests that this inhibitory effect on neutrophil functions exists during therapeutic use.
D012898:Autacoids / Q000097:blood*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D066298:In Vitro Techniques; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*
D012898:Autacoids; D002121:Calcium Channel Blockers; D010972:Platelet Activating Factor; D011725:Pyridines; D005966:Glucuronidase; D009543:Nifedipine; D002118:Calcium