Catestatin (CgA344-364) stimulates rat mast cell release of histamine in a manner comparable to mastoparan and other cationic charged neuropeptides

Catestatin (bovine CgA(344-364)) is a cationic peptide, which besides reducing catecholamine secretion from chromaffin cells in vitro also acts a potent vasodilator in the rat in vivo. The alleged histamine releasing effect of catestatin was tested in vitro in rat mast cells. The most active domain of catestatin (bovine CgA(344-358): RSMRLSFRARGYGFR) caused concentration-dependent (0.01-5 microM) release of histamine from peritoneal and pleural mast cells. The potency and efficacy of catestatin was higher than for the wasp venom peptide, mastoparan. Only in the pleural cells was neurotensin (NT) more potent than catestatin, mastoparan and substance P (SP), consistent with a receptor-mediated histamine release by neurotensin. Amongst these cationic peptides, substance P was least effective. The acidic CgA peptide (WE-14, bovine CgA (324-337)) neither stimulated nor modulated histamine release by the cationic peptides. The catestatin and neurotensin evoked histamine release were suppressed by pertussis toxin (PTX), suggesting involvement of a G(i) subunit. Electron micrographs of rat pleural mast cells responding to catestatin revealed a concentration-dependent discharge of granular material. We propose that catestatin activates histamine release from rat mast cells by a mechanism analogous to that already established for mastoparan and other amphiphilic cationic neuropeptides (the peptidergic pathway) and distinct from the mechanism of inhibition of catecholamine release from chromaffin cells.