Histamine H1-receptor-mediated keratan sulfate production in rabbit chondrocytes: involvement of protein kinase C.
We investigated the characteristics of the histamine H1-receptor in cultured rabbit chondrocytes. Scatchard analysis of [3H]pyrilamine, an H1-antagonist, binding to the chondrocytes revealed a single class of binding sites with KD and Bmax values of 90 +/- 12 nM and 56 +/- 11 fmol/10(4) cells, respectively. H1-agonists stimulated the production of keratan sulfate in a dose-dependent manner. Stimulation of keratan sulfate production was inhibited by pyrilamine. Protein kinase C inhibitors (sphingosine and H-7) also had inhibitory effects. Phorbol 12,13-dibutyrate, a direct activator of protein kinase C, activated the production. When protein kinase C in the chondrocytes was down-regulated by preincubation with phorbol ester, the effect of the H1-agonist on keratan sulfate production was abolished. These results indicate that the histamine H1-receptor on chondrocytes mediates the accumulation of keratan sulfate production and that protein kinase C is involved in these events.
Fukuda
K
K
Department of Orthopedic Surgery, Kinki University School of Medicine, Osaka, Japan.
Yamasaki
H
H
Nagata
Y
Y
Motoyoshi
H
H
Matsumura
F
F
Kuno
T
T
Tanaka
S
S
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D002744:Chlorpheniramine / Q000494:pharmacology*; D007632:Keratan Sulfate / Q000096:biosynthesis*; D007700:Kinetics; D008761:Methylhistamines / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011738:Pyrilamine / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000502:physiology*; D013110:Sphingosine / Q000494:pharmacology
D008761:Methylhistamines; D011969:Receptors, Histamine H1; D015240:Phorbol 12,13-Dibutyrate; D002744:Chlorpheniramine; D007632:Keratan Sulfate; D011493:Protein Kinase C; C026259:2-methylhistamine; D011738:Pyrilamine; D013110:Sphingosine