title: Inhibition of histamine H1 receptor downregulation by KT5823, a protein kinase G inhibitor.
abstract: The role of various protein kinases in the downregulation of histamine H(1) receptors was studied by using their inhibitors and activators. Human histamine H(1) receptors (H(1)Rs) expressed in CHO cells were downregulated by histamine in a dose- and time-dependent manner, and this downregulation continued to increase over a 24-h period. KT5823, an inhibitor of protein kinase G, remarkably but not completely reversed the histamine-induced H(1)R downregulation over 24 h. HA1004, another inhibitor of protein kinase G, showed a similar inhibitory effect. However, both 8-Br-cGMP and 8-pCPT-cGMP, membrane-permeable analogues of cGMP, did not show any effects on H(1)R downregulation in the absence or presence of histamine. Ro 31-8220, an inhibitor of protein kinase C (PKC), did not affect histamine-induced downregulation of H(1)R; nor did phorbol 12-myristate 13-acetate, a PKC-activating phorbol ester. Similarly, histamine-induced downregulation of H(1)R was unaffected by either H-89, an inhibitor of protein kinase A, or 8-Br-cAMP, a membrane-permeable analogue of cAMP.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokushima, Tokushima, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Miyoshi
authors.forename: N
authors.initials: N
authors.lastname: Kawakami
authors.forename: S
authors.initials: S
authors.lastname: Horio
authors.forename: H
authors.initials: H
authors.lastname: Fukui
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002227:Carbazoles / Q000494:pharmacology*; D006224:Cricetinae; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D015536:Down-Regulation; D020536:Enzyme Activators / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011969:Receptors, Histamine H1 / Q000096:biosynthesis / Q000187:drug effects*; D013449:Sulfonamides; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors
chemical_list: D002227:Carbazoles; D020536:Enzyme Activators; D007211:Indoles; D007546:Isoquinolines; D011969:Receptors, Histamine H1; D013449:Sulfonamides; D013873:Thionucleotides; C073601:KT 5823; D015124:8-Bromo Cyclic Adenosine Monophosphate; C055656:8-((4-chlorophenyl)thio)cyclic-3',5'-GMP; D006632:Histamine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D011493:Protein Kinase C; D006152:Cyclic GMP; C064758:Ro 31-8220