title: Novel mastoparan analogs induce differential secretion from mast cells.
abstract: Cationic amphiphilic peptides stimulate secretion via a receptor-independent action upon G proteins. We have previously utilized chimeric analogs of mastoparan (MP), including galparan (galanin(1-13)-MP ), as molecular probes of secretion. 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 beta-hexosaminidase. Peptide-induced activation of phospholipase D (PLD), an enzyme intimately involved in regulated exocytosis [5], correlated with the secretion of beta-hexosaminidase but not 5-HT. Thus, these data indicate that different mechanisms are responsible for the exocytosis of 5-HT and beta-hexosaminidase, respectively. Moreover, mastoparan analogs are novel tools for probing the molecular details of exocytosis and other biological phenomena.
authors.affiliation: Molecular Pharmacology Group, School of Health Sciences, University of Wolverhampton, 62-68 Lichfield Street, WV1 1DJ, Wolverhampton, United Kingdom.
authors.forename: Michelle
authors.initials: M
authors.lastname: Farquhar
authors.forename: Ursel
authors.initials: U
authors.lastname: Soomets
authors.forename: Ruth L
authors.initials: RL
authors.lastname: Bates
authors.forename: Ashley
authors.initials: A
authors.lastname: Martin
authors.forename: Ulo
authors.initials: U
authors.lastname: Langel
authors.forename: John
authors.initials: J
authors.lastname: Howl
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D002460:Cell Line; D015195:Drug Design; D036341:Intercellular Signaling Peptides and Proteins; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship; D014862:Wasp Venoms / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D014862:Wasp Venoms; C037500:mastoparan