Mastoparan-induced phosphatidylcholine hydrolysis by phospholipase D activation in human astrocytoma cells.

Abstract

1. The effect of mastoparan on phosphatidylcholine hydrolysis was examined in 1321N1 human astrocytoma cells. Mastoparan (3-30 microM) caused an accumulation of diacylglycerol (DG) and phosphatidic acd (PA) accompanied by choline release in a concentration- and time-dependent manner. 2. In the presence of 2% n-butanol, mastoparan (3-100 microM) induced phosphatidylbutanol (PBut) accumulation in a concentration- and time-dependent manner, suggesting that mastoparan activates phospholipase D (PLD). Propranolol (30-300 microM), a phosphatidate phosphohydrolase inhibitor, inhibited DG accumulation induced by mastoparan, supporting this idea. 3. Depletion of extracellular free calcium ion did not alter the effect of mastoparan on PLD activity. 4. A protein kinase C (PKC) inhibitor, calphostin C (1 microM), did not inhibit mastoparan-induce PLD activation but the ability of mastoparan to stimulate phospholipase D activity was decreased in the PKC down regulated cells. 5. PLD activity stimulated by mastoparan was not prevented by pretreatment of the cells with pertussis toxin (PT) or C3 ADP-ribosyltransferase. Furthermore, guanine nucleotides did not affect PLD activity stimulation by mastoparan in membrane preparations. 6. Mastoparan stimulated PLD in several cell lines such as RBL-2H3, RBL-1, HL-60, P388, endothelial cells, as well as 1321N1 human astrocytoma cells. 7. These results suggest that mastoparan induces phosphatidylcholine (PC) hydrolysis by activation of PLD, not by activation of phosphatidylcholine-specific phospholipase C (PC-PLC); mastoparan-induced PLD activation is not mediated by G proteins.

• Authors: K Mizuno, N Nakahata, Y Ohizumi
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 116 Issue 3 Pg. 2090-6 (Oct 1995) ISSN: 0007-1188 [Print] England
• PMID: 8640350 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Intercellular Signaling Peptides and Proteins
• Peptides
• Phosphatidylcholines
• Wasp Venoms
• mastoparan
• Propranolol
• Phospholipase D

Topics

• Animals
• Astrocytoma (enzymology, metabolism)
• Dose-Response Relationship, Drug
• Enzyme Activation (drug effects)
• Humans
• Hydrolysis (drug effects)
• Intercellular Signaling Peptides and Proteins
• Peptides
• Phosphatidylcholines (metabolism)
• Phospholipase D (metabolism)
• Propranolol (pharmacology)
• Time Factors
• Tumor Cells, Cultured
• Wasp Venoms (pharmacology)