Histamine release from human basophils by pepstatin A

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Abstract
Pepstatin A, a pentapeptide isolated from cultures of actinomycetes, induced histamine secretion from human basophils in the concentration range of 3×10−7 to 10−4M. The characteristics of this reaction were similar to those of f-met-peptide-induced histamine release: pepstatin A-induced release required Ca2+ and the release reaction was complete within 2 min at 22 or 37°C, but did not occur at 4°C. Release by both pepstatin a and f-met-peptide was reversibly inhibited by two non-releasing analogs of f-met-peptide, CBZ-Phe-Met and BOC-Met-Leu-Phe, Further, there was complete cross-desensitization between pepstatin A and f-met-peptide, while cells desensitized to pepstatin A released normally with anti-IgE and vice versa. A variety of pharmacological agents had similar effects on both pepstatin A and f-met-peptide-induced release (e.g., no enhancement with D2O; marked enhancement with cytochalasin B). We suggest that pepstatin A induces histamine release from human basophils by activating a cell surface receptor(s), also activated by the synthetic tripeptide f-met-peptide.