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.