Histamine H2 receptor mediates keratan sulfate secretion in rabbit chondrocytes: role of cAMP

Abstract

We obtained evidence for the presence of a single class of histamine H2 receptor on rabbit chondrocytes. Stimulation of these receptors with specific H2 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 H2 histamine receptor.