Effects of phospholipase A(2) activating peptides upon GTP-binding protein-evoked adrenocorticotrophin secretion

A GTP-binding protein (G-protein), termed G-exocytosis (Ge), mediates the e ffects of calcium ions in the late stages of the adrenocorticotrophin (ACTH ) secretory pathway. An activator of Ge, mastoparan, also stimulates phosph olipase A(2) and so a comparison of other phospholipase A(2)-activating pep tides, melittin and phospholipase A(2)-activating peptide was made with mas toparan to assess whether phospholipase A(2)activation was an important com ponent of Ge-evoked secretion. All three peptides stimulated ACTH secretion in the effective absence of calcium ions from permeabilised cells, actions potentiated by a phospholipase A(2)inhibitor. Ca2+-evoked secretion from p ermeabilised cells was similarly potentiated by a phospholipase A, inhibito r. Furthermore, arachidonic acid inhibited Ca2+- and Ge-evoked ACTH secreti on, an action blocked by the cyclo-oxygenase inhibitor ibuprofen. This stud y suggests that the products of phospholipase A(2)-generated arachidonic me tabolism may exert an inhibitory action on the late post-Ca2+ stages of the ACTH secretory pathway and that prostaglandins may be the active agents in this capacity. (C) 2001 Elsevier Science B.V. All rights reserved.