Cross-talk between receptor-regulated phospholipase D and phospholipase C in brain.
Because receptors, G proteins, and phospholipases all exist within a membrane lipid environment, it is not unreasonable to assume that an enzyme capable of changing the lipid environment can affect the coupling relationship among these signal transducing components. Our previous study showed that a muscarinic acetylcholine receptor regulates phosphatidylcholine phospholipase D via a G protein in brain. We demonstrate here that phosphatidylinositol phospholipase C and phosphatidylcholine phospholipase D are simultaneously activated within 15 s by muscarine in the presence of 1 microM GTP gamma S. More important, inhibition of phospholipase D by zinc attenuated carbamylcholine-induced activation of phospholipase C by 30%. Our additional evidence strongly indicates that the receptor-regulated phospholipase D plays an important modulatory role in agonist-stimulated phosphatidylinositol breakdown. This modulatory effect may be achieved by changing the membrane microenvironment in which phospholipase C and phosphoinositol lipids reside, consequently amplifying the inositol phospholipid signaling process. Our results lead us to postulate that the potential interaction between two different signaling pathways may provide a cell with intracellular coordination and enable the cell to achieve functional responses.
Qian
Z
Z
Department of Biochemistry and Molecular Biology, School of Medicine, University of Minnesota, Duluth 55812.
Drewes
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LR
D000818:Animals; D001921:Brain / Q000201:enzymology*; D004285:Dogs; D009116:Muscarine / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000378:metabolism; D010739:Phospholipase D / Q000032:analysis*; D011976:Receptors, Muscarinic / Q000502:physiology*; D010738:Type C Phospholipases / Q000032:analysis*; D015032:Zinc / Q000494:pharmacology
D010713:Phosphatidylcholines; D011976:Receptors, Muscarinic; D009116:Muscarine; D010738:Type C Phospholipases; D010739:Phospholipase D; D015032:Zinc