HISTAMINE-H2-RECEPTOR MEDIATES KERATAN SULFATE SECRETION IN RABBIT CHONDROCYTES - ROLE OF CAMP

We obtained evidence for the presence of a single class of histamine H-2 receptor on rabbit chondrocytes. Stimulation of these receptors with specific H-2 agonists led to an inhibition of keratan sulfate secretion and rapid (15 min) accumulation of intracellular adenosine 3',5'-cyclic monophosphate (cAMP). Factors such as prostaglandin E2 and parathyroid hormone, which stimulate short-term increases in cAMP, also caused a reduction in keratan sulfate secretion. Conversely, cholera toxin and forskolin, which enhance cAMP accumulation over 48 and 4 h, respectively, as well as a continuous exposure to dibutyryl cAMP, stimulated keratan sulfate secretion. These data suggest that intracellular cAMP must be kept above a certain level for a prolonged period to stimulate keratan sulfate secretion. We conclude that inhibition of keratan sulfate secretion is coupled with activation of the H-2 histamine receptor.