Coincidence detection at the level of phospholipase C activation mediated by the m4 muscarinic acetylcholine receptor
| Autor: | Ernest G. Peralta, Reed C. Carroll, Anthony D. Morielli |
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| Rok vydání: | 1995 |
| Předmět: |
Transcription
Genetic G protein CHO Cells Biology General Biochemistry Genetics and Molecular Biology Adenosine Triphosphate GTP-Binding Proteins Cricetinae Muscarinic acetylcholine receptor Muscarinic acetylcholine receptor M5 Animals Receptor Agricultural and Biological Sciences(all) Phospholipase C Biochemistry Genetics and Molecular Biology(all) Purinergic receptor Receptors Purinergic Genes fos Muscarinic acetylcholine receptor M1 Receptors Muscarinic Cell biology Enzyme Activation Biochemistry Type C Phospholipases Calcium Signal transduction General Agricultural and Biological Sciences Signal Transduction |
| Zdroj: | Current Biology. 5:536-544 |
| ISSN: | 0960-9822 |
| DOI: | 10.1016/s0960-9822(95)00106-0 |
| Popis: | Background: One of the principal mechanisms by which G-protein-coupled receptors evoke cellular responses is through the activation of phospholipase C (PLC) and the subsequent release of Ca 2+ from intracellular stores. Receptors that couple to pertussis toxin (PTX)-insensitive G proteins typically evoke large increases in PLC activity and intracellular Ca 2+ release. In contrast, receptors that use only PTX-sensitive G proteins usually generate weak PLC-dependent responses, but efficiently regulate a second effector enzyme, adenylyl cyclase. For example, in many cell types, agonist binding by the m4 muscarinic acetylcholine receptor (m4 receptor) results in a strong inhibition of adenylyl cyclase and very little stimulation of PLC activity or release of intracellular Ca 2+ . We have investigated whether the weak, PTX-sensitive stimulation of PLC activity by the m4 receptor can play a significant role in the generation of cellular responses. Results We report here that PTX-sensitive Ca 2+ release mediated by the m4 receptor in transfected Chinese hamster ovary cells is greatly enhanced when endogenous purinergic receptors simultaneously activate a PTX-insensitive signaling pathway. Furthermore, m4-receptor-induced transcription of the c-fos gene (a Ca 2+ -sensitive response) is similarly potentiated when purinergic receptors are coactivated. These enhanced m4-receptor-dependent Ca 2+ responses do not require an influx of external Ca 2+ , and occur in the absence of detectable purinergic-receptor-stimulated Ca 2+ release; they apparently require the activation of both PTX-sensitive and PTX-insensitive G-protein pathways. Measurements of phosphoinositide hydrolysis indicate that the enhancement of m4-receptor-mediated Ca 2+ signaling by purinergic receptors is due to a synergistic increase in agonist-stimulated PLC activity. Conclusion These studies demonstrate that the potency of m4-receptor-mediated PLC signaling is highly dependent upon the presence or absence of other PLC-activating agonists. The ability of the m4 receptor to evoke a strong, but conditional, activation of PLC may allow this type of receptor to participate in a coincidence-detection system that amplifies simultaneous PLC-activating signals through a mechanism involving crosstalk between PTX-sensitive and PTX-insensitive G-protein pathways. |
| Databáze: | OpenAIRE |
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