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Miyoshi K, Kawakami N, Horio S, Fukui H. Methods Find Exp Clin
Pharmacol. 2003 Jun;25(5):343-7
Inhibition of histamine H1 receptor downregulation by
KT5823, a protein kinase G inhibitor.
Department of Pharmacology, Faculty of Pharmaceutical
Sciences, University of Tokushima, Tokushima, Japan.
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. (c) 2003 Prous
Science. All rights reserved.
PMID: 12851655 |
