title: Is protein kinase C involved in histamine H1-receptor desensitization?
abstract: Histamine H1-receptor mediated effects in guinea-pig lung and intestine appear to desensitize homologously rather rapidly. Within a few minutes of exposure to a high concentration of histamine (30-100 microM) the c-GMP production in guinea-pig lung and the contraction of guinea-pig jejunum are markedly attenuated. In both tissues the responses to other stimulating agents (e.g. muscarinic agent, calcium ionophore) are not affected. The protein kinase C (PKC) activating phorbolester phorbol-12,13- dibutyrate (PDB) concentration-dependently depresses H1-receptor responses in both tissues. Yet, PDB does not only attenuate the H1-receptor responses but also affects responses to other stimulating agents. In the guinea-pig ileum muscarinic receptor mediated contractions are inhibited equipotently by PDB, whereas in lung tissue the c-GMP formation after calcium-ionophore addition is affected too. In view of these findings the possible role of PKC in H1-receptor desensitization is discussed.
authors.affiliation: Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Leurs
authors.forename: M J
authors.initials: MJ
authors.lastname: Smit
authors.forename: M M
authors.initials: MM
authors.lastname: Brozius
authors.forename: W
authors.initials: W
authors.lastname: Jansen
authors.forename: A
authors.initials: A
authors.lastname: Bast
authors.forename: H
authors.initials: H
authors.lastname: Timmerman
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D004361:Drug Tolerance; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D015759:Ionomycin / Q000494:pharmacology; D007583:Jejunum / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011969:Receptors, Histamine H1 / Q000187:drug effects* / Q000502:physiology
chemical_list: D011969:Receptors, Histamine H1; D016210:Methacholine Chloride; D015240:Phorbol 12,13-Dibutyrate; D015759:Ionomycin; D006632:Histamine; D011493:Protein Kinase C; D006152:Cyclic GMP