Is protein kinase C involved in histamine H1-receptor desensitization?
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.
Leurs
R
R
Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, The Netherlands.
Smit
M J
MJ
Brozius
M M
MM
Jansen
W
W
Bast
A
A
Timmerman
H
H
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
D011969:Receptors, Histamine H1; D016210:Methacholine Chloride; D015240:Phorbol 12,13-Dibutyrate; D015759:Ionomycin; D006632:Histamine; D011493:Protein Kinase C; D006152:Cyclic GMP