Further characterization of the synergistic activation mechanism of cationic channels by M2 and M3 muscarinic receptors in mouse intestinal smooth muscle cells
| Autor: | Masayuki Yamamoto, Toshihiro Unno, Noriko Inasaki, Yasuyuki Tanahashi, Mai Uchiyama, Taisuke Katsurada, Seiichi Komori, Hayato Matsuyama, Takashi Sakamoto |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cell signaling Phospholipase C Physiology Chemistry G protein 05 social sciences Cell Biology Neuropeptide Y receptor Cell biology 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology Chelerythrine Calphostin C Muscarinic acetylcholine receptor 0501 psychology and cognitive sciences 050102 behavioral science & comparative psychology Phosphatidylinositol |
| Zdroj: | American Journal of Physiology-Cell Physiology. 318:C514-C523 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.00277.2019 |
| Popis: | In mouse ileal myocytes, muscarinic receptor-mediated cationic current ( mIcat) occurs mainly through synergism of M2 and M3 subtypes involving Gi/o-type GTP-binding proteins and phospholipase C (PLC). We have further studied the M2/M3 synergistic pathway. Carbachol-induced mIcat was markedly depressed by YM-254890, a Gq/11 protein inhibitor. However, the mIcat was unaffected by heparin, calphostin C, or chelerythrine, suggesting that mIcat activation does not involve signaling molecules downstream of phosphatidylinositol 4,5-bisphosphate (PIP2) breakdown. M2-knockout (KO) mice displayed a reduced mIcat (~10% of wild-type mIcat) because of the lack of M2-Gi/o signaling. The impaired mIcat was insensitive to neuropeptide Y possessing a Gi/o-stimulating activity. M3-KO mice also displayed a reduced mIcat (~6% of wild-type mIcat) because of the lack of M3-Gq/11 signaling, and the mIcat was insensitive to prostaglandin F2α possessing a Gq/11-stimulating activity. These results suggest the importance of Gq/11/PLC-hydrolyzed PIP2 breakdown itself in mIcat activation and also support the idea that the M2/M3 synergistic pathway represents a signaling complex consisting of M2-Gi/o and M3-Gq/11-PLC systems in which both G proteins are special for this pathway but not general in receptor coupling. |
| Databáze: | OpenAIRE |
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