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.
Zamani
M R
MR
School of Biological Sciences, Division of Neuroscience, University of Manchester, England.
Dupere
J R
JR
Bristow
D R
DR
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000819:agonists / Q000378:metabolism*; D006632:Histamine / Q000502:physiology; D007295:Inositol Phosphates / Q000096:biosynthesis*; D007425:Intracellular Membranes / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D009994:Osmolar Concentration; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011969:Receptors, Histamine H1 / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007295:Inositol Phosphates; D011969:Receptors, Histamine H1; D006632:Histamine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium