Essential thiol and disulphide groups in the histamine H1-receptor signal transfer of guinea-pig parenchymal lung strips.
Guinea-pig parenchymal lung strips contract after H1-receptor stimulation and membrane depolarisation with KCl. Contractions after 50 mM KCl were similar to the maximal histamine response. Treatment of lung strips with micromolar concentrations of the thiol-alkylator N-ethylmaleimide markedly affects both histamine H1-receptor mediated and 50 mM KCl-induced contractions. The H1-receptor response was only affected via a decrease in the maximal response. The response to 50 mM KCl was also inhibited after thiol-alkylation. However, H1-receptor responses appeared to be slightly more sensitive towards thiol-alkylation compared to KCl-responses. Reduction of disulphide groups with 1,4-dithiothreitol also modified the contractile responses to both stimuli. It is concluded that both thiol- and disulphide moieties play important roles in the regulation of histamine H1-receptor activity.
Leurs
R
R
Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, The Netherlands.
Bast
A
A
Timmerman
H
H
D000818:Animals; D004220:Disulfides / Q000494:pharmacology*; D004229:Dithiothreitol / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D004220:Disulfides; D011969:Receptors, Histamine H1; D013438:Sulfhydryl Compounds; D011189:Potassium Chloride; D005033:Ethylmaleimide; D004229:Dithiothreitol