Homologous desensitization of bombesin-induced increases in intracellular Ca2+ in quiescent Swiss 3T3 cells involves a protein kinase C-independent mechanism

J Cell Physiol. 1993 Aug;156(2):333-40. doi: 10.1002/jcp.1041560216.

Abstract

Addition of bombesin to Swiss 3T3 cells causes a rapid and transient increase in the intracellular concentration of Ca2+ ([Ca2+]i), which is followed by desensitization to a subsequent addition of the peptide. The concentrations of bombesin used to study this acute cellular desensitization (0.1-0.5 nM) did not deplete the intracellular pool of Ca2+ released by inositol(1,4,5)trisphosphate, as shown by addition of vasopressin after consecutive additions of bombesin. Two lines of evidence support the conclusion that activation of protein kinase C (PKC) does not mediate the acute homologous desensitization of Ca2+ responses induced by bombesin. First, long-term treatment (48 h) of Swiss 3T3 cells with phorbol 12,13-dibutyrate (PDB) to deplete PKC did not prevent homologous desensitization. The responses to second additions of bombesin at 0.1, 0.25, and 0.5 nM were 42%, 26% and 11% of the initial responses, respectively. Second, the PKC inhibitor GF 109203X did not alter homologous desensitization at concentrations that completely prevented the inhibition of Ca2+ mobilization induced by PDB and blocked PDB-mediated phosphorylation of the prominent PKC substrate 80K/MARCKS. We conclude that acute homologous desensitization of Ca2+ responses induced by bombesin occurs through a PKC-independent mechanism.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells / drug effects*
  • Animals
  • Bombesin / metabolism
  • Bombesin / pharmacology*
  • Calcium / analysis
  • Calcium / metabolism*
  • Cell Division
  • Dose-Response Relationship, Drug
  • Down-Regulation / physiology
  • Feedback
  • Indoles / pharmacology
  • Iodine Radioisotopes
  • Maleimides / pharmacology
  • Mice
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Precipitin Tests
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / physiology*
  • Receptors, Bombesin
  • Receptors, Neurotransmitter / analysis
  • Receptors, Neurotransmitter / metabolism
  • Receptors, Neurotransmitter / physiology
  • Signal Transduction / physiology
  • Vasopressins / pharmacology

Substances

  • Indoles
  • Iodine Radioisotopes
  • Maleimides
  • Receptors, Bombesin
  • Receptors, Neurotransmitter
  • Vasopressins
  • Phorbol 12,13-Dibutyrate
  • Protein Kinase C
  • bisindolylmaleimide I
  • Bombesin
  • Calcium