Am. J. Respir. Cell Mol. Biol., Vol 12, No. 4, Apr 1995, 416-424.
Histamine provokes turnover of inositol phospholipids in guinea pig and human airway epithelial cells via an H1-receptor/G protein-dependent mechanism
H Li, NH Choe, DT Wright and KB Adler
Department of Anatomy, Physiological Sciences and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA.
Guinea pig tracheal epithelial cells in primary air/liquid interface
culture (GPTE) and virally transformed human bronchial epithelial cells
(BEAS-2B) were exposed to histamine at concentrations of 1 to 100 microM.
At concentrations greater than 1 microM, histamine elicited a
concentration-dependent increase in accumulation of inositol phosphates in
both cell types, as assessed by anion exchange chromatography. The effects
of histamine were most pronounced at 15 to 30 min and were attenuated by
the H1-receptor antagonist, pyrilamine. The H2-receptor antagonist,
ranitidine, was without effect. Sodium fluoride (25 mM), a
non-receptor-associated activator of GTP binding (G) proteins, increased
accumulation of inositol phosphates within GPTE and BEAS cells. In cells
permeabilized with digitonin, the nonhydrolyzable GTP analog,
guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S; 10 microM) increased
inositol phosphate accumulation. This GTP gamma S-induced increase was
attenuated by exposure to 500 microM guanosine-5'-O-(2- thiodiphosphate)
(GDP beta S). Additionally, histamine-induced increases in inositol
phosphate accumulation were potentiated by GTP gamma S and attenuated by
GDP beta S. These data indicate involvement of a G protein in the response
to histamine. Preincubation with pertussis toxin (100 ng/ml for 4 h) did
not significantly affect the response, suggesting that the associated G
protein was not pertussis toxin-sensitive. The presence of the
phosphatidylinositol-specific phospholipase C (PI-PLC)-associated G
protein, G alpha q/11, and the presence of mRNA for the Gq family, were
ascertained by immunoblotting and Northern hybridization,
respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
