Islet‐activating protein, pertussis toxin, inhibits Ca²⁺‐induced and guanine nucleotide‐dependent releases of histamine and arachidonic acid from rat mast cells

Abstract

Islet‐activating protein Guanine nucleotide‐binding protein Ca2+ Histamine secretion Arachidonic acid

Pertussis toxin does not affect the time course of exocytosis in mast cells stimulated by intracellular application of GTP‐γ‐S

“…We now demonstrate that the time course is also affected by the intracellular calcium concentration. In contrast to previous results [9] we found that IAP-treated cells which lost their responsiveness to stimulation with compound 48/80 still respond normally to intracellular application of GTP-7-S. This result supports the existence of a second GTP-binding protein GE [10,11] which directly controls exocytosis in mast ceils.…”

“…Since lAP ADP-ribosylates at least 3 different GTP-binding proteins [16,17] it was suggested that a G-protein might be the substrate of IAP in mast cells [6]. Calcium-dependent release of histamine and arachidonic acid from GPP(NH)P-loaded mast cells has also been reported to be partially inhibited by lAP [9] and by neomycin which is an inhibitor of the polyphosphoinositide phospholipase C [7]. These results were in agreement with the involvement of a single G-protein (Gp) regulating stimulus-secretion coupling in mast ceils.…”

Comparison of histamine release induced by synthetic polycations with that by compound 48/80 from rat mast cells.

“…This activation is inhibited by pretreatment of the mast cells with IAP, which also inhibits histamine release from basophils (6,18,19), although cholera toxin potentiates serotonin release from basophil leukemia cells, but does not affect histamine release from mast cells (20,21). We found that IAP inhibited histamine release induced by all the polycations we tested, except PEI18, suggesting that the histamine releases induced by some polycations seemed to be mediated by G protein, like the release by compound 48/80 (Fig.…”

Pertussis toxin inhibits fMet-Leu-Phe- but not phorbol ester-stimulated changes in rabbit neutrophils: role of G proteins in excitation response coupling.

“…16 and 17; unpublished observations). Second, the incorporation of guanine nucleotides into permeabilized mast cells causes secretion in response to the subsequent addition of Ca2+ (18,19), and this release is inhibited by pertussis toxin (19).The present studies were undertaken to investigate the role of protein kinase C in the regulation of the activity of the Na+/H+ antiport and to examine the effect of pertussis toxin on the stimulated biochemical changes in rabbit neutrophils. The results reported here clearly show that (i) phorbol 12-myristate 13-acetate (PMA) activates the Na+/H+ antiport system, and (ii) the addition of pertussis toxin inhibits the fMet-Leu-Phe but not the PMA-induced increase in Na+-influx, the increase in intracellular pH, and the changes in lipid metabolism and protein phosphorylation.…”