Neomycin inhibits histamine and thapsigargin mediated Ca2+ entry in DDT1 MF-2 cells independent of phospholipase C activation.
The histamine H1 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 microM) 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)P3) 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 Ca(2+)-ATPase by thapsigargin (1 microM), 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.
Sipma
H
H
Groningen Institute for Drug Studies (GIDS), Department of Clinical Pharmacology, University of Groningen, Netherlands.
Van der Zee
L
L
Den Hertog
A
A
Nelemans
A
A
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D006224:Cricetinae; D004789:Enzyme Activation / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009355:Neomycin / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011969:Receptors, Histamine H1 / Q000502:physiology; D019284:Thapsigargin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*; D014649:Vas Deferens / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism
D006634:Histamine H1 Antagonists; D011500:Protein Synthesis Inhibitors; D011969:Receptors, Histamine H1; C028521:lanthanum chloride; D016718:Arachidonic Acid; D019284:Thapsigargin; D007811:Lanthanum; D006632:Histamine; D010738:Type C Phospholipases; D000252:Calcium-Transporting ATPases; D009355:Neomycin; D002118:Calcium