Osmo-mechanically sensitive phosphatidylinositol signaling regulates a Ca2+ influx channel in renal epithelial cells.

摘要: Regulation of dihydropyridine (nifedipine)-sensitive calcium influx was studied in rabbit culture proximal tubule cells using the fura 2 fluorescence ratio technique. "Osmo-mechanically induced" swelling by exposure to hypotonic medium (220 mosmol/kgH2O) caused a rapid rise intracellular that predominantly due via both dihydropyridine-sensitive (nifedipine-sensitive) and -insensitive pathways. The pathway regulated, part, phosphatidylinositol signaling pathway. Inhibition phospholipase C treatment with 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (NCDC), inhibition protein kinase (PKC) staurosporine, or long-term (24 h) phorbol 12-myristate 13-acetate (PMA) downregulate PKC abolished most osmo-induced, signal. Short-term (seconds) PMA activate produced marked stimulation isotonic (2- 3-fold stimulation) (5-fold conditions. In contrast, elevation adenosine 3',5'-cyclic monophosphate (cAMP) forskolin A (PKA) cAMP analog, Rp-8-CPT-cAMPS (the Rp diastereoisomer monophosphothionate), had little no influence on influx, including influx. It is concluded osmo-mechanical stress activates dihyropyridine-sensitive regulated not through cAMP/PKA