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 effects of calcium ions in the late stages of the adrenocorticotrophin (ACTH) secretory pathway. An activator of Ge, mastoparan, also stimulates phospholipase A(2) and so a comparison of other phospholipase A(2)-activating peptides, melittin and phospholipase A(2)-activating peptide was made with mastoparan to assess whether phospholipase A(2)activation was an important component 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. Ca(2+)-evoked secretion from permeabilised cells was similarly potentiated by a phospholipase A(2) inhibitor. Furthermore, arachidonic acid inhibited Ca(2+)- and Ge-evoked ACTH secretion, an action blocked by the cyclo-oxygenase inhibitor ibuprofen. This study suggests that the products of phospholipase A(2)-generated arachidonic metabolism may exert an inhibitory action on the late post-Ca(2+) stages of the ACTH secretory pathway and that prostaglandins may be the active agents in this capacity.
Guild
S B
SB
Molecular Endocrinology Group, School of Biology, Bute Medical Building, University of St. Andrews, St. Andrews, KY16 9TS, UK. sbg@st-andrews.ac.uk
D000324:Adrenocorticotropic Hormone / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002463:Cell Membrane Permeability; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007052:Ibuprofen / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D008555:Melitten / Q000494:pharmacology; D010455:Peptides; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011506:Proteins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014862:Wasp Venoms / Q000494:pharmacology
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011506:Proteins; D014862:Wasp Venoms; C055324:phospholipase A2-activating protein; C081565:arachidonyltrifluoromethane; D008555:Melitten; D016718:Arachidonic Acid; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C037500:mastoparan; D000324:Adrenocorticotropic Hormone; D010741:Phospholipases A; D019204:GTP-Binding Proteins; D002118:Calcium; D007052:Ibuprofen