Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Calcium / physiology
-
Calcium-Transporting ATPases / antagonists & inhibitors
-
Cell Line
-
Cimetidine / pharmacology
-
Cystic Fibrosis
-
Enzyme Activation / drug effects
-
Enzyme Inhibitors / pharmacology
-
Epithelium / enzymology
-
GTP-Binding Proteins / physiology
-
Histamine / pharmacology*
-
Histamine H1 Antagonists / pharmacology
-
Histamine H2 Antagonists / pharmacology
-
Humans
-
Inositol Phosphates / metabolism
-
Pertussis Toxin
-
Protein Kinase C / physiology
-
Pyrilamine / pharmacology
-
Receptors, Histamine H1 / physiology*
-
Signal Transduction / drug effects
-
Thapsigargin / pharmacology
-
Trachea / cytology
-
Trachea / enzymology*
-
Type C Phospholipases / metabolism*
-
Virulence Factors, Bordetella / pharmacology
Substances
-
Enzyme Inhibitors
-
Histamine H1 Antagonists
-
Histamine H2 Antagonists
-
Inositol Phosphates
-
Receptors, Histamine H1
-
Virulence Factors, Bordetella
-
Thapsigargin
-
Cimetidine
-
Histamine
-
Pertussis Toxin
-
Protein Kinase C
-
Type C Phospholipases
-
GTP-Binding Proteins
-
Calcium-Transporting ATPases
-
Pyrilamine
-
Calcium