Desensitization of the histamine H_1-receptor and transcriptional down-regulation of histamine H_1-receptor gene expression in bovine tracheal smooth muscle

摘要

We have investigated the role of protein kinase C(PKC) in the desensitization of histamine H_1- receptors and in the expression of the histamine H_1-receptor gene in airway smooth muscle. Prolonged 4β-phorbol 12,13 dibutyrate(PDBu) pretreatment(4 h, 100 nM-1 μM) of bovine Trachealis caused a concentration-dependent loss of contraction in response to histamine H-1-receptor Stimulation, which was associated with a concentration-dependent decrease in histamine-induced total [~3H]-inositol phosphates accumulation. In contrast, the responses to sodium fluoride a direct G-protein activator, were unalterd by PDBu(100-300 nM) pre-incubation and only slightly reduced following incubation with 1 μM PDBu.