Electrogenic arginine transport mediates stimulus-secretion coupling in mouse pancreatic beta-cells

J Physiol. 1997 Mar 15;499 ( Pt 3)(Pt 3):625-35. doi: 10.1113/jphysiol.1997.sp021955.

Abstract

1. We have investigated the mechanism by which L-arginine stimulates membrane depolarization, an increase of intracellular calcium ([Ca2+]i) and insulin secretion in pancreatic beta-cells. 2. L-Arginine failed to affect beta-cell metabolism, as monitored by NAD(P)H autofluorescence. 3. L-Arginine produced a dose-dependent increase in [Ca2+]i, which was dependent on membrane depolarization and extracellular calcium. 4. The cationic amino acids L-ornithine, L-lysine, L-homoarginine (which is not metabolized) and NG-monomethyl-L-arginine (L-NMMA, a nitric oxide synthase inhibitor) produced [Ca2+]i responses similar to that produced by L-arginine. The neutral nitric oxide synthase inhibitors NG-nitro-L-arginine (L-NNA) and N omega-monomethyl-L-arginine (L-NAME) also increased [Ca2+]i. D-Arginine was ineffective. 5. L-Arginine did not affect whole-cell Ca2+ currents or ATP-sensitive K+ currents, but produced an inward current that was carried by the amino acid. 6. The reverse transcriptase-polymerase chain reaction demonstrated the presence of messenger RNA for the murine cationic amino acid transporters mCAT2A and mCAT2B within the beta-cell. 7. L-Arginine did not affect beta-cell exocytosis as assayed by changes in cell capacitance. 8. Our data suggest that L-arginine elevates [Ca2+]i and stimulates insulin secretion as a consequence of its electrogenic transport into the beta-cell. This uptake is mediated by the mCAT2A transporter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Aniline Compounds / metabolism
  • Animals
  • Arginine / analogs & derivatives
  • Arginine / metabolism*
  • Biological Transport
  • Calcium / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Electric Conductivity
  • Enzyme Inhibitors / pharmacology
  • Exocytosis
  • Fluorescent Dyes / metabolism
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / metabolism*
  • Kinetics
  • Membrane Glycoproteins*
  • Membrane Potentials
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitroarginine / pharmacology
  • RNA, Messenger / metabolism
  • Receptors, Virus*
  • Xanthenes / metabolism
  • omega-N-Methylarginine / pharmacology

Substances

  • Aniline Compounds
  • Carrier Proteins
  • Enzyme Inhibitors
  • Fluorescent Dyes
  • Insulin
  • Membrane Glycoproteins
  • Membrane Proteins
  • RNA, Messenger
  • Receptors, Virus
  • Xanthenes
  • ecotropic murine leukemia virus receptor
  • Nitroarginine
  • Fluo-3
  • omega-N-Methylarginine
  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase
  • Calcium
  • NG-Nitroarginine Methyl Ester