Guanylyl cyclase C ameliorates visceral pain: an unsuspected link
Visceral pain associated with irritable bowel syndrome afflicts 15% of the US population. Although treatments are limited, guanylyl cyclase C (GUCY2C) agonists alleviate pain and constipation. Until now, it was assumed that the activation of GUCY2C and production of cGMP in enterocytes stimulated fl...
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| Format: | Article |
| Language: | English |
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American Society for Clinical Investigation
2023-02-01
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| Series: | The Journal of Clinical Investigation |
| Online Access: | https://doi.org/10.1172/JCI166703 |
| _version_ | 1797634492398043136 |
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| author | Rodger A. Liddle |
| author_facet | Rodger A. Liddle |
| author_sort | Rodger A. Liddle |
| collection | DOAJ |
| description | Visceral pain associated with irritable bowel syndrome afflicts 15% of the US population. Although treatments are limited, guanylyl cyclase C (GUCY2C) agonists alleviate pain and constipation. Until now, it was assumed that the activation of GUCY2C and production of cGMP in enterocytes stimulated fluid secretion and reduced visceral sensation. The recent discovery that a subtype of enteroendocrine cells (EECs) known as neuropod cells synapse with submucosal neurons unveiled a pathway for communicating gut signals to the nervous system. In this issue of the JCI, Barton et al. report that GUCY2C is enriched in neuropod cells and is involved with sensory nerve firing. Selective deletion of GUCY2C in mouse models suggests that defective GUCY2C neuropod–cell signaling underlies visceral pain. These studies introduce possibilities for dissociating the secretory and analgesic effects of GUCY2C agonism. Although further work remains, unveiling the role of neuropod cells is a major step in understanding visceral pain. |
| first_indexed | 2024-03-11T12:08:35Z |
| format | Article |
| id | doaj.art-3824a2f8d8444b5d87284c8fd2fde29c |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-03-11T12:08:35Z |
| publishDate | 2023-02-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-3824a2f8d8444b5d87284c8fd2fde29c2023-11-07T16:19:57ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382023-02-011334Guanylyl cyclase C ameliorates visceral pain: an unsuspected linkRodger A. LiddleVisceral pain associated with irritable bowel syndrome afflicts 15% of the US population. Although treatments are limited, guanylyl cyclase C (GUCY2C) agonists alleviate pain and constipation. Until now, it was assumed that the activation of GUCY2C and production of cGMP in enterocytes stimulated fluid secretion and reduced visceral sensation. The recent discovery that a subtype of enteroendocrine cells (EECs) known as neuropod cells synapse with submucosal neurons unveiled a pathway for communicating gut signals to the nervous system. In this issue of the JCI, Barton et al. report that GUCY2C is enriched in neuropod cells and is involved with sensory nerve firing. Selective deletion of GUCY2C in mouse models suggests that defective GUCY2C neuropod–cell signaling underlies visceral pain. These studies introduce possibilities for dissociating the secretory and analgesic effects of GUCY2C agonism. Although further work remains, unveiling the role of neuropod cells is a major step in understanding visceral pain.https://doi.org/10.1172/JCI166703 |
| spellingShingle | Rodger A. Liddle Guanylyl cyclase C ameliorates visceral pain: an unsuspected link The Journal of Clinical Investigation |
| title | Guanylyl cyclase C ameliorates visceral pain: an unsuspected link |
| title_full | Guanylyl cyclase C ameliorates visceral pain: an unsuspected link |
| title_fullStr | Guanylyl cyclase C ameliorates visceral pain: an unsuspected link |
| title_full_unstemmed | Guanylyl cyclase C ameliorates visceral pain: an unsuspected link |
| title_short | Guanylyl cyclase C ameliorates visceral pain: an unsuspected link |
| title_sort | guanylyl cyclase c ameliorates visceral pain an unsuspected link |
| url | https://doi.org/10.1172/JCI166703 |
| work_keys_str_mv | AT rodgeraliddle guanylylcyclasecamelioratesvisceralpainanunsuspectedlink |