Add time:08/07/2019         Source:sciencedirect.com

Cationic amphiphilic peptides stimulate secretion via a receptor-independent action upon G proteins [1]. We have previously utilized chimeric analogs of mastoparan (MP), including galparan (galanin(1–13)-MP [2]), as molecular probes of secretion 3, 4. Here, we further resolve the structure-activity relationship of peptidyl secretagogs, including rationally designed chimeric MP analogs. The secretory efficacies of 10 MP analogs were significantly higher than 45 unrelated basic peptides. Comparative studies identified MP analogs that are differential secretagogs for 5-hydroxytryptamine (5-HT) and β-hexosaminidase. Peptide-induced activation of phospholipase D (PLD), an enzyme intimately involved in regulated exocytosis [5], correlated with the secretion of β-hexosaminidase but not 5-HT. Thus, these data indicate that different mechanisms are responsible for the exocytosis of 5-HT and β-hexosaminidase, respectively. Moreover, mastoparan analogs are novel tools for probing the molecular details of exocytosis and other biological phenomena.

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