Receptor‐Mediated Desensitisation of Histamine H1 Receptor‐Stimulated Inositol Phosphate Production and Calcium Mobilisation in GT1‐7 Neuronal Cells Is Independent of Protein Kinase C

: GT1‐7 cells, a clonal line derived from specific tumours of gonadotropin‐releasing hormone‐secreting neurons from mouse hypothalamus, were used as a model system to investigate the cellular mechanisms underlying the histamine H1 receptor‐mediated desensitisation. GT1‐7 cells contain H1 receptors, acute stimulation of which leads to the desensitisation of histamine‐mediated calcium mobilisation and is manifest as a concurrent reduction in both the magnitude of the calcium transient and of the sustained phase. Acute pretreatment of the cells with the phorbol ester, phorbol 12‐myristate 13‐acetate, can also ablate the histamine‐stimulated calcium mobilisation. In addition, acute H1‐receptor stimulation and acute phorbol ester treatment result in the attenuation of histamine‐mediated inositol phosphate production. Receptor desensitisation resulting from acute stimulation with histamine is not affected by inhibiting protein kinase C (PKC) activity with Ro 31‐7549 or staurosporine. In contrast, the desensitisation of H1‐receptor responses induced by direct activation of protein kinase C is preventable by PKC inhibitors. Thus, these results imply that a PKC‐dependent mechanism and PKC‐independent mechanism are involved in the H1‐receptor desensitisation cascade in GT1‐7 cells and do not support the involvement of PKC in the receptor‐mediated desensitisation of H1 receptor‐stimulated calcium and inositol phosphate responses.