The site of action of the histamine releaser compound 45/80 in causing mast cell degranulation.

A primary amine analog of compound 48/80 (nor-48/80) was purified and attached to Sepharose beads through an albumin link. Suspensions of rat peritoneal cells were passed over the beads in an affinity chromatography column, and the proportion of the mast cells that was retained by the beads was determined. Sixty-seven percent of the mast cells were found to be retained by the column, indicating the existence of a binding site for nor-48/80 on the exterior of mast cells. The beads were larger than the cells, and hence precluded the entry of the nor-48/80 into the cells. Neither the Sepharose beads nor the albumin link was responsible for this amount of binding because control beads without nor-48-80 retained only 22% of the mast cells. Mast cells incubated with large quantities of the beads in a batch procedure released up to 53% of the mast cell histamine, whereas control beads without the polymer released only 18%. This release could not be attributable to soluble nor-48/80 because only trace amounts of radioactive nor-48/80 were released from beads soaked overnight, and these supernatants released insignificant amounts of histamine when incubated with mast cells. These studies indicate the presence of a receptor for 48/80 on the mast cell membrane which can trigger histamine release.