Histamine activates phosphorylase and inositol phosphate production in guinea pig hepatocytes.
In guinea pig hepatocytes, histamine increased phosphorylase activity and inositol phosphate production. Similar effects were obtained with 2-(2-aminoethyl)-thiazole, a histamine H1 receptor agonist, but not with dimaprit or impromidine, H2 receptor agonists. These effects of histamine were dose-dependently inhibited by the H1 antihistamines, (+)-chlorpheniramine and mepyramine (pyrilamine) but not by cimetidine or ranitidine, H2 antagonists. (+)-Chlorpheniramine and mepyramine had similar potencies (apparent Ki values approximately 3 nM) when incubated with the cells for 1 min (phosphorylase a assays) but the former was 15-20-fold more potent than the latter at longer incubation times (apparent Ki values approximately 3-4 nM and 45-90 nM, respectively) indicating that mepyramine is actively metabolized by guinea pig hepatocytes. Histamine increased cytosol calcium approximately 2-fold, an effect also mediated through H1 receptors. The actions of histamine were not affected by in vivo ADP-ribosylation by pertussis toxin. Our data clearly indicate that histamine modulates the metabolism of guinea pig hepatocytes via activation of H1 receptors. These receptors are coupled to the phosphoinositide turnover-calcium mobilization signalling pathway through a pertussis toxin-insensitive process.
García-Sáinz
J A
JA
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, D.F., Mexico.
Macías-Silva
M
M
Olivares-Reyes
A
A
Romero-Avila
M T
MT
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010762:Phosphorylase a / Q000378:metabolism*; D011969:Receptors, Histamine H1 / Q000187:drug effects
D017442:Histamine Agonists; D006633:Histamine Antagonists; D007295:Inositol Phosphates; D011969:Receptors, Histamine H1; D006632:Histamine; D010762:Phosphorylase a