title: Prostaglandin E1 inhibits endocytosis in the β-cell endocytosis.
abstract: Prostaglandins inhibit insulin secretion in a manner similar to that of norepinephrine (NE) and somatostatin. As NE inhibits endocytosis as well as exocytosis, we have now examined the modulation of endocytosis by prostaglandin E1 (PGE1). Endocytosis following exocytosis was recorded by whole-cell patch clamp capacitance measurements in INS-832/13 cells. Prolonged depolarizing pulses producing a high level of Ca(2+) influx were used to stimulate maximal exocytosis and to deplete the readily releasable pool (RRP) of granules. This high Ca(2+) influx eliminates the inhibitory effect of PGE1 on exocytosis and allows specific characterization of the inhibitory effect of PGE1 on the subsequent compensatory endocytosis. After stimulating exocytosis, endocytosis was apparent under control conditions but was inhibited by PGE1 in a Pertussis toxin-sensitive (PTX)-insensitive manner. Dialyzing a synthetic peptide mimicking the C-terminus of the α-subunit of the heterotrimeric G-protein Gz into the cells blocked the inhibition of endocytosis by PGE1, whereas a control-randomized peptide was without effect. These results demonstrate that PGE1 inhibits endocytosis and Gz mediates the inhibition.
authors.affiliation: Department of Molecular MedicineCornell University, Ithaca, New York, USA School of Applied and Engineering PhysicsCornell University, Ithaca, New York, USA Laboratory for Nanoscale Cell BiologyMax-Planck-Institute for Biophysical Chemistry, Goettingen, Germany.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: School of Applied and Engineering PhysicsCornell University, Ithaca, New York, USA Laboratory for Nanoscale Cell BiologyMax-Planck-Institute for Biophysical Chemistry, Goettingen, Germany.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Fang
authors.affiliation: Department of Molecular MedicineCornell University, Ithaca, New York, USA.
authors.forename: Susanne G
authors.initials: SG
authors.lastname: Straub
authors.affiliation: School of Applied and Engineering PhysicsCornell University, Ithaca, New York, USA Laboratory for Nanoscale Cell BiologyMax-Planck-Institute for Biophysical Chemistry, Goettingen, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Lindau
authors.affiliation: Department of Molecular MedicineCornell University, Ithaca, New York, USA gws2@cornell.edu.
authors.forename: Geoffrey W G
authors.initials: GW
authors.lastname: Sharp
mesh_terms: D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D020013:Calcium Signaling; D002460:Cell Line; D004705:Endocytosis / Q000187:drug effects*; D005089:Exocytosis / Q000187:drug effects; D044385:GTP-Binding Protein alpha Subunits / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D051381:Rats
chemical_list: D044385:GTP-Binding Protein alpha Subunits; C490963:Gnaz protein, rat; D007328:Insulin; D010446:Peptide Fragments; D037342:Pertussis Toxin; D000527:Alprostadil
keywords: endocytosis; heterotrimeric G-protein Gz; prostaglandin E1; β-cells