| 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
(Affiliation: Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.)
|
| Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 116
Issue 3
Pg. 2090-6
(Oct 1995)
ISSN: 0007-1188 ENGLAND |
| PMID | 8640350
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Peptides
- Phosphatidylcholines
- Wasp Venoms
- Propranolol
- mastoparan
- Phospholipase D
|
| Topics |
- Animals
- Astrocytoma
(enzymology, metabolism)
- Dose-Response Relationship, Drug
- Enzyme Activation
(drug effects)
- Humans
- Hydrolysis
(drug effects)
- Peptides
- Phosphatidylcholines
(metabolism)
- Phospholipase D
(metabolism)
- Propranolol
(pharmacology)
- Time Factors
- Tumor Cells, Cultured
- Wasp Venoms
(pharmacology)
|
