title: Hormonal inhibition of endocytosis: novel roles for noradrenaline and G protein G(z).
abstract: The modulation of endocytosis following exocytosis by noradrenaline (NA), a physiological inhibitor of insulin secretion, was investigated in INS 832/13 cells using patch-clamp capacitance measurements. Endocytosis was inhibited by NA in a pertussis toxin-insensitive manner. Dialysing a synthetic peptide mimicking the C-terminus of the α-subunit of G(z) into the cells blocked the inhibition of endocytosis by NA. Cell-attached capacitance measurements indicated that inhibition by NA was due to a decreased number of endocytotic events without a change in vesicle size. Analysis of fission pore closure kinetics revealed two distinct fission modes, with NA selectively inhibiting the rapid fission pore closure events. Comparison of the actions of NA and deltamethrin, a calcineurin antagonist and potent inhibitor of endocytosis, demonstrated that they inhibit endocytosis by different mechanisms. These findings establish novel actions for NA and G(z) in insulin-secreting cells and possibly other cell types.
authors.affiliation: Department of Molecular Medicine, Cornell University, Ithaca, NY 14853-6401, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Fang
authors.forename: Susanne G
authors.initials: SG
authors.lastname: Straub
authors.forename: Manfred
authors.initials: M
authors.lastname: Lindau
authors.forename: Geoffrey W G
authors.initials: GW
authors.lastname: Sharp
mesh_terms: D000818:Animals; D002460:Cell Line; D025802:Electric Capacitance; D004705:Endocytosis / Q000187:drug effects* / Q000502:physiology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007306:Insecticides / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D021122:Protein Subunits; D011722:Pyrethrins / Q000494:pharmacology; D022161:Transport Vesicles / Q000187:drug effects / Q000502:physiology
chemical_list: D007306:Insecticides; D009570:Nitriles; D021122:Protein Subunits; D011722:Pyrethrins; C017180:decamethrin; D019204:GTP-Binding Proteins; D009638:Norepinephrine