Neomycin inhibits histamine and thapsigargin mediated Ca2+ DDT1 MF-2 cells independent of phospholipase C activation

H Sipma, L VanderZee, A DenHertog, A Nelemans

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Scopus)

Abstract

The histamine H-1 receptor mediated increase in cytoplasmic Ca2+ ([Ca2+](i)) was measured in the presence of the known phospholipase C (PLC) inhibitor, neomycin. Neomycin (1 mM) inhibited the histamine (100 mu M) induced rise in [Ca2+](i) to the same extent as observed after blocking Ca2+ entry with LaCl3. Likewise, the increase in [Ca2+](i) after re-addition of CaCl2 (2 mM) to extracellular Ca2+ deprived and histamine pretreated cells was strongly reduced by neomycin. However, neomycin did not inhibit the histamine induced formation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P-3) or the release of Ca2+ from internal stores. These results show that neomycin blocks histamine induced Ca2+ entry independent of phospholipase C activation. Inhibition of intracellular store Ca2+-ATPase by thapsigargin (1 mu M), elicited an increase in [Ca2+](i) due to a leakage from the stores, subsequently followed by store-dependent Ca2+ entry. Thapsigargin induced Ca2+ entry was also completely blocked by neomycin. These results indicate that neomycin inhibits histamine and thapsigargin induced Ca2+ entry. This inhibition is most likely exerted at the level of plasma membrane Ca2+ channels.

Original languageEnglish
Pages (from-to)207-212
Number of pages6
JournalEuropean Journal of Pharmacology
Volume305
Issue number1-3
Publication statusPublished - 3-Jun-1996

Keywords

  • histamine H-1 receptor
  • neomycin
  • Ca2+ entry
  • phospholipase C
  • INOSITOL 1,3,4,5-TETRAKISPHOSPHATE
  • PLASMA-MEMBRANE
  • CALCIUM INFLUX
  • SMOOTH-MUSCLE
  • CHANNELS
  • STORES
  • CA-2+
  • MESSENGER
  • PROLIFERATION
  • TRISPHOSPHATE

Cite this