Regulation of histamine H1 receptor-mediated phosphoinositide hydrolysis by histamine and phorbol esters in DDT1 MF-2 cells

Matthew S. Cowlen, Michael R. Barnes, Myron L. Toews

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The regulation of histamine-stimulated phosphoinositide turnover by histamine and phorbol esters was examined in intact DDT1 MF-2 cells grown in suspension culture. Histamine increased the incorporation of 32P into phosphatidylinositol (PI) in these cells, and this stimulation was inhibited by the H1 antagonist diphenhydramine but not by the H2 antagonist cimetidine. Pretreatment of cells with histamine or with phorbol 12-myristate 13-acetate (PMA) or other activators of protein kinase C induced a marked decrease in the subsequent stimulation by histamine. PMA, but not histamine, also decreased the ability of epinephrine to stimulate PI labelling through α1-adrenoceptors. Thus, histamine appears to induce homologous desensitization of histamine H1 receptor-mediated PI turnover, whereas direct activation of protein kinase C in the absence of receptor occupancy by agonist induces nonspecific heterologous desensitization of both histamine H1- and α1-adrenoceptor-mediated responses.

Original languageEnglish (US)
Pages (from-to)105-112
Number of pages8
JournalEuropean Journal of Pharmacology: Molecular Pharmacology
Volume188
Issue number2-3
DOIs
StatePublished - Mar 13 1990

Fingerprint

Histamine H1 Receptors
Phorbol Esters
Phosphatidylinositols
Histamine
Hydrolysis
Adrenergic Receptors
Protein Kinase C
Acetates
Diphenhydramine
Cimetidine
Epinephrine
Suspensions

Keywords

  • Desensitization
  • Histamine receptors
  • Phosphoinositide hydrolysis
  • Protein kinase C

ASJC Scopus subject areas

  • Pharmacology

Cite this

Regulation of histamine H1 receptor-mediated phosphoinositide hydrolysis by histamine and phorbol esters in DDT1 MF-2 cells. / Cowlen, Matthew S.; Barnes, Michael R.; Toews, Myron L.

In: European Journal of Pharmacology: Molecular Pharmacology, Vol. 188, No. 2-3, 13.03.1990, p. 105-112.

Research output: Contribution to journalArticle

@article{8fd8620eb3dd41e497d411d7cfdc9ed4,
title = "Regulation of histamine H1 receptor-mediated phosphoinositide hydrolysis by histamine and phorbol esters in DDT1 MF-2 cells",
abstract = "The regulation of histamine-stimulated phosphoinositide turnover by histamine and phorbol esters was examined in intact DDT1 MF-2 cells grown in suspension culture. Histamine increased the incorporation of 32P into phosphatidylinositol (PI) in these cells, and this stimulation was inhibited by the H1 antagonist diphenhydramine but not by the H2 antagonist cimetidine. Pretreatment of cells with histamine or with phorbol 12-myristate 13-acetate (PMA) or other activators of protein kinase C induced a marked decrease in the subsequent stimulation by histamine. PMA, but not histamine, also decreased the ability of epinephrine to stimulate PI labelling through α1-adrenoceptors. Thus, histamine appears to induce homologous desensitization of histamine H1 receptor-mediated PI turnover, whereas direct activation of protein kinase C in the absence of receptor occupancy by agonist induces nonspecific heterologous desensitization of both histamine H1- and α1-adrenoceptor-mediated responses.",
keywords = "Desensitization, Histamine receptors, Phosphoinositide hydrolysis, Protein kinase C",
author = "Cowlen, {Matthew S.} and Barnes, {Michael R.} and Toews, {Myron L.}",
year = "1990",
month = "3",
day = "13",
doi = "10.1016/0922-4106(90)90045-Y",
language = "English (US)",
volume = "188",
pages = "105--112",
journal = "European Journal of Pharmacology - Molecular Pharmacology Section",
issn = "0922-4106",
publisher = "Elsevier BV",
number = "2-3",

}

TY - JOUR

T1 - Regulation of histamine H1 receptor-mediated phosphoinositide hydrolysis by histamine and phorbol esters in DDT1 MF-2 cells

AU - Cowlen, Matthew S.

AU - Barnes, Michael R.

AU - Toews, Myron L.

PY - 1990/3/13

Y1 - 1990/3/13

N2 - The regulation of histamine-stimulated phosphoinositide turnover by histamine and phorbol esters was examined in intact DDT1 MF-2 cells grown in suspension culture. Histamine increased the incorporation of 32P into phosphatidylinositol (PI) in these cells, and this stimulation was inhibited by the H1 antagonist diphenhydramine but not by the H2 antagonist cimetidine. Pretreatment of cells with histamine or with phorbol 12-myristate 13-acetate (PMA) or other activators of protein kinase C induced a marked decrease in the subsequent stimulation by histamine. PMA, but not histamine, also decreased the ability of epinephrine to stimulate PI labelling through α1-adrenoceptors. Thus, histamine appears to induce homologous desensitization of histamine H1 receptor-mediated PI turnover, whereas direct activation of protein kinase C in the absence of receptor occupancy by agonist induces nonspecific heterologous desensitization of both histamine H1- and α1-adrenoceptor-mediated responses.

AB - The regulation of histamine-stimulated phosphoinositide turnover by histamine and phorbol esters was examined in intact DDT1 MF-2 cells grown in suspension culture. Histamine increased the incorporation of 32P into phosphatidylinositol (PI) in these cells, and this stimulation was inhibited by the H1 antagonist diphenhydramine but not by the H2 antagonist cimetidine. Pretreatment of cells with histamine or with phorbol 12-myristate 13-acetate (PMA) or other activators of protein kinase C induced a marked decrease in the subsequent stimulation by histamine. PMA, but not histamine, also decreased the ability of epinephrine to stimulate PI labelling through α1-adrenoceptors. Thus, histamine appears to induce homologous desensitization of histamine H1 receptor-mediated PI turnover, whereas direct activation of protein kinase C in the absence of receptor occupancy by agonist induces nonspecific heterologous desensitization of both histamine H1- and α1-adrenoceptor-mediated responses.

KW - Desensitization

KW - Histamine receptors

KW - Phosphoinositide hydrolysis

KW - Protein kinase C

UR - http://www.scopus.com/inward/record.url?scp=0025259526&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025259526&partnerID=8YFLogxK

U2 - 10.1016/0922-4106(90)90045-Y

DO - 10.1016/0922-4106(90)90045-Y

M3 - Article

C2 - 2156711

AN - SCOPUS:0025259526

VL - 188

SP - 105

EP - 112

JO - European Journal of Pharmacology - Molecular Pharmacology Section

JF - European Journal of Pharmacology - Molecular Pharmacology Section

SN - 0922-4106

IS - 2-3

ER -