NEOMYCIN INHIBITS HISTAMINE AND THAPSIGARGIN MEDIATED CA2-2 CELLS INDEPENDENT OF PHOSPHOLIPASE-C ACTIVATION( DDT1 MF)

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 bloc king Ca2+ entry with LaCl3. Likewise, the increase in [Ca2+](i) after re-addition of CaCl2 (2 mM) to extracellular Ca2+ deprived and histami ne pretreated cells was strongly reduced by neomycin. However, neomyci n did not inhibit the histamine induced formation of inositol 1,4,5-tr isphosphate (Ins(1,4,5)P-3) or the release of Ca2+ from internal store s. These results show that neomycin blocks histamine induced Ca2+ entr y independent of phospholipase C activation. Inhibition of intracellul ar 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 c ompletely blocked by neomycin. These results indicate that neomycin in hibits histamine and thapsigargin induced Ca2+ entry. This inhibition is most likely exerted at the level of plasma membrane Ca2+ channels.