Histamine activates phospholipase C in human airway epithelial cells via a phorbol ester-sensitive pathway.
In human airway epithelial cell lines 9HTEo- and CFNPE9o, histamine causes a transient elevation of intracellular free calcium concentration ([Ca2+]i) detected by fura 2 fluorescence, which is due to both release from intracellular stores and extracellular Ca2+ entry. The effect of histamine is abolished by the Ca(2+)-ATPase inhibitor thapsigargin. Histamine also stimulates inositol phosphate accumulation. Changes in [Ca2+]i and inositol phosphate production exhibit a similar dose-response relationship for histamine (maximal effect at 10(-4) M), with both phenomena being blocked by the H1 antagonist mepyramine and being insensitive to pertussis toxin treatment. The effects of histamine on phosphoinositide metabolism and [Ca2+]i are abolished by a short-term preincubation with phorbol ester, and this effect is reversed by staurosporine and calphostin C, suggesting a feedback regulation by protein kinase C. The results indicate that human airway epithelial cells contain H1 receptors coupled to phospholipase C through a pertussis toxin-insensitive G protein.
Rugolo
M
M
Departmento di Biologia Ev.Sp., Universitá di Bologna, Italy.
Barzanti
F
F
Gruenert
D C
DC
Hrelia
S
S
D002118:Calcium / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002460:Cell Line; D002927:Cimetidine / Q000494:pharmacology; D003550:Cystic Fibrosis; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000201:enzymology; D019204:GTP-Binding Proteins / Q000502:physiology; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000502:physiology; D011738:Pyrilamine / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D019284:Thapsigargin / Q000494:pharmacology; D014132:Trachea / Q000166:cytology / Q000201:enzymology*; D010738:Type C Phospholipases / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D007295:Inositol Phosphates; D011969:Receptors, Histamine H1; D010566:Virulence Factors, Bordetella; D019284:Thapsigargin; D002927:Cimetidine; D006632:Histamine; D037342:Pertussis Toxin; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D000252:Calcium-Transporting ATPases; D011738:Pyrilamine; D002118:Calcium