{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Brierley SM"],"funding":["Ironwood Pharmaceuticals, Incorporated","NIDDK NIH HHS","National Health and Medical Research Council","NINDS NIH HHS","National Institutes of Health","Australian Research Council"],"pagination":["110-122"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8760167"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["43(2)"],"pubmed_abstract":["Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habit that affects ~11% of the global population. Over the past decade, preclinical and clinical studies have revealed a variety of novel mechanisms relating to the visceral analgesic effects of guanylate cyclase-C (GC-C) agonists. Here we discuss the mechanisms by which GC-C agonists target the GC-C/cyclic guanosine-3',5'-monophosphate (cGMP) pathway, resulting in visceral analgesia as well as clinically relevant relief of abdominal pain and other sensations in IBS patients. Due to the preponderance of evidence we focus on linaclotide, a 14-amino acid GC-C agonist with very low oral bioavailability that acts within the gut. Collectively, the weight of experimental and clinical evidence supports the concept that GC-C agonists act as peripherally acting visceral analgesics."],"journal":["Trends in pharmacological sciences"],"pubmed_title":["Guanylate cyclase-C agonists as peripherally acting treatments of chronic visceral pain."],"pmcid":["PMC8760167"],"funding_grant_id":["R01 DK122280","DK 122280","R01 DK115950","1U01NS113871-01","U01 NS113869","R01 115950","1U01NS113869-01","DP180101395","U01 NS113871"],"pubmed_authors":["Camilleri M","Castro J","Harrington AM","Brierley SM","Grundy L","Hannig G"],"additional_accession":[]},"is_claimable":false,"name":"Guanylate cyclase-C agonists as peripherally acting treatments of chronic visceral pain.","description":"Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habit that affects ~11% of the global population. Over the past decade, preclinical and clinical studies have revealed a variety of novel mechanisms relating to the visceral analgesic effects of guanylate cyclase-C (GC-C) agonists. Here we discuss the mechanisms by which GC-C agonists target the GC-C/cyclic guanosine-3',5'-monophosphate (cGMP) pathway, resulting in visceral analgesia as well as clinically relevant relief of abdominal pain and other sensations in IBS patients. Due to the preponderance of evidence we focus on linaclotide, a 14-amino acid GC-C agonist with very low oral bioavailability that acts within the gut. Collectively, the weight of experimental and clinical evidence supports the concept that GC-C agonists act as peripherally acting visceral analgesics.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Feb","modification":"2025-04-19T17:57:25.295Z","creation":"2025-04-19T17:57:25.295Z"},"accession":"S-EPMC8760167","cross_references":{"pubmed":["34865885"],"doi":["10.1016/j.tips.2021.11.002"]}}