title: Modulatory action of potassium channel openers on field potential and histamine release from rat peritoneal mast cells.
abstract: To determine whether changes in membrane potential affect the extent of mast cell degranulation, compound 48/80 was added to rat peritoneal mast cell suspensions in the absence or presence of potassium channel openers (KCOs). Changes were compared between the field potential (FP) and the amount of histamine released. The results demonstrated that (i) the onset and duration of FP, which reflects the hyperpolarizing nature of the response, increased as the concentration of compound 48/80 increased; (ii) both FP and the amount of histamine released increased as the concentration of compound 48/80 increased; (iii) although both KCOs (SDZ PCO400, a benzopyran derivative, and P1060, a cyanoguanidine derivative) potentiated compound 48/80-induced increases in FP and histamine release, without compound 48/80, they had no effect on either parameter; (iv) both glibenclamide and charybdotoxin significantly attenuated the compound 48/80-induced increase in FP; and (v) glibenclamide was able to attenuate the KCO-induced potentiation of FP. The results show that drugs presumably causing hyperpolarization can affect histamine release from rat peritoneal mast cells. The effect of KCOs on compound 48/80-induced response appears to be potentiation in nature rather than synergism. It is possible that KCO hyperpolarizes the cell membrane, enhances Ca2+ influx, and thus increases histamine release. As such, selective blockers of K+ channels may be useful for the treatment of immunological disorders.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong. yeungck@rocketmail.com
authors.forename: Chi-Kong
authors.initials: CK
authors.lastname: Yeung
authors.forename: Jessica Ka-Yan
authors.initials: JK
authors.lastname: Law
authors.forename: Sze-Wing
authors.initials: SW
authors.lastname: Sam
authors.forename: Sven
authors.initials: S
authors.lastname: Ingebrandt
authors.forename: Hang-Yung Alaster
authors.initials: HY
authors.lastname: Lau
authors.forename: John Anthony
authors.initials: JA
authors.lastname: Rudd
authors.forename: Mansun
authors.initials: M
authors.lastname: Chan
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D003517:Cyclopentanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects / Q000502:physiology*; D054086:KATP Channels / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010537:Peritoneum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
chemical_list: D001578:Benzopyrans; D003517:Cyclopentanes; D006146:Guanidines; D054086:KATP Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; C073091:SDZ PCO 400; D003189:p-Methoxy-N-methylphenethylamine; C058754:N'-cyano-N-(3-pyridyl)-N''-(t-butyl)guanidine