title: Histamine provokes turnover of inositol phospholipids in guinea pig and human airway epithelial cells via an H1-receptor/G protein-dependent mechanism.
abstract: 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)
authors.affiliation: Department of Anatomy, Physiological Sciences and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: N H
authors.initials: NH
authors.lastname: Choe
authors.forename: D T
authors.initials: DT
authors.lastname: Wright
authors.forename: K B
authors.initials: KB
authors.lastname: Adler
mesh_terms: D000328:Adult; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000502:physiology*; D015870:Gene Expression; D006168:Guinea Pigs; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism*; D037342:Pertussis Toxin; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010716:Phosphatidylinositols / Q000378:metabolism*; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011969:Receptors, Histamine H1 / Q000502:physiology*; D015398:Signal Transduction; D012969:Sodium Fluoride / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D012333:RNA, Messenger; D011969:Receptors, Histamine H1; D010566:Virulence Factors, Bordetella; D012969:Sodium Fluoride; D037342:Pertussis Toxin; D010727:Phosphoric Diester Hydrolases; D054801:Phosphoinositide Phospholipase C; D019204:GTP-Binding Proteins; D043265:Phosphatidylinositol Diacylglycerol-Lyase