title: Inhibitory effects of local anesthetics on migration, extracellular release of lysosomal enzyme, and superoxide anion production in human polymorphonuclear leukocytes.
abstract: This study examined the effects of four typical local anesthetics, lidocaine, prilocaine, procaine and tetracaine, on the functioning of human polymorphonuclear leukocytes (PMN). PMN were stimulated by fMet-Leu-Phe (FMLP) or phorbol myristate acetate (PMA) to elicit chemotaxis, extracellular release of beta-glucuronidase (BGL) and superoxide anion (SOA) production. The four agents inhibited chemotaxis efficiently and in a concentration-dependent manner but had only weak effects on the release of BGL. The effect of tetracaine was strongest, followed by lidocaine, then prilocaine, whereas the effect of procaine was blunt. The 50% inhibitory concentrations (IC50 in molarity) of the four local anesthetics for chemotaxis were as follows: tetracaine = 4.1 x 10(-4), lidocaine = 3.2 x 10(-3), prilocaine = 3.6 x 10(-3), procaine = 4.9 x 10(-3), those for SOA production induced by FMLP were: tetracaine = 3.1 x 10(-4), lidocaine = 5.9 x 10(-3), prilocaine = 1.9 x 10(-2), procaine = 1.2 x 10(-2), those for SOA production induced by PMA were: tetracaine = 1.1 x 10(-3), lidocaine = 1.2 x 10(-2), prilocaine = 1.5 x 10(-2), procaine = 2.5 x 10(-2), and those for release of BGL were: tetracaine = 1.6 x 10(-3), lidocaine = 5.3 x 10(-3), prilocaine = 2.8 x 10(-2), procaine = 1.2 x 10(-1). The IC50 seemed to relate to the anesthetic's chemical structures and their inhibitory properties on PMN functions, as lidocaine and prilocaine, which are aminoamide type anesthetics, preferentially inhibited chemotaxis, whereas tetracaine and procaine, aminoester type anesthetics, inhibited SOA production induced by FMLP. The results suggest that the inhibitory effects of local anesthetics on human PMN functions are also correlated with local anesthetic potency and vary according to differences in their chemical structures.
authors.affiliation: Department of Pathology, Radiation Effects Research Foundation, Hiroshima, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Sasagawa
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008247:Lysosomes / Q000201:enzymology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D013481:Superoxides / Q000378:metabolism*
chemical_list: D000779:Anesthetics, Local; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D005966:Glucuronidase