Activation of histamine H1 receptor results in enhanced proteoglycan synthesis by human articular chondrocyte: involvement of protein kinase C and intracellular Ca(2+).
In earlier work, we obtained evidence for the presence of histamine H1 and H2 receptors on chondrocytes. Activation of the H1 receptor enhanced keratan sulfate synthesis, and protein kinase C (PKC) inhibitors antagonized histamine-stimulated keratan sulfate (KS) synthesis. These data do indicate the involvement of PKC in activation of H1 receptor, but precise mechanisms remained to be clarified. Human articular chondrocytes were treated with different concentrations of histamine and its antagonist. Intracellular Ca(2+) and proteoglycan synthesis was measured, using the fluorescent indicator dye Fura-2 AM and [35S]-sulfate incorporation, respectively. Activation of the H1 receptor led to stimulation of proteoglycan synthesis and evoked increases in levels of intracellular Ca(2+). Activity of PKC was also enhanced with activation of the H1 receptor. Intracellular Ca(2+) and activation of PKC are involved in the signal transduction pathway of H1 receptor-mediated stimulation of proteoglycan synthesis.
Sohen
Satoshi
S
Department of Orthopaedic Surgery, Kinki University School of Medicine, Ohnohigashi 377-2, Osaka-sayama, 589, Osaka, Japan
Ooe
Hisayuki
H
Hashima
Makoto
M
Nonaka
Tohgo
T
Fukuda
Kanji
K
Hamanishi
Chiaki
C