Cyclic Nucleotide Concentrations of Rectal Mucosa in Ulcerative Colitis

Zlatkina, A R; Belousova, Elena; Vinitsky, L. I.; Avtandilov, G. G.; Chervonnaya, L. V.

doi:10.3109/00365529009095496

Cited by 3 publications

(1 citation statement)

References 12 publications

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“…As previously discussed, activating mutations in GC-C are associated with IBD, supporting the observation that higher levels of mucosal cGMP are maintained in inflammatory states ( 10 , 16 , 250 ). An animal model of a gain-of-function mutation in GC-C confirmed these clinical observations ( 13 ).…”

Section: Learning Opportunities and Prospectssupporting

confidence: 78%

Receptor Guanylyl Cyclase C and Cyclic GMP in Health and Disease: Perspectives and Therapeutic Opportunities

2022

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Receptor Guanylyl Cyclase C (GC-C) was initially characterized as an important regulator of intestinal fluid and ion homeostasis. Recent findings demonstrate that GC-C is also causally linked to intestinal inflammation, dysbiosis, and tumorigenesis. These advances have been fueled in part by identifying mutations or changes in gene expression in GC-C or its ligands, that disrupt the delicate balance of intracellular cGMP levels and are associated with a wide range of clinical phenotypes. In this review, we highlight aspects of the current knowledge of the GC-C signaling pathway in homeostasis and disease, emphasizing recent advances in the field. The review summarizes extra gastrointestinal functions for GC-C signaling, such as appetite control, energy expenditure, visceral nociception, and behavioral processes. Recent research has expanded the homeostatic role of GC-C and implicated it in regulating the ion-microbiome-immune axis, which acts as a mechanistic driver in inflammatory bowel disease. The development of transgenic and knockout mouse models allowed for in-depth studies of GC-C and its relationship to whole-animal physiology. A deeper understanding of the various aspects of GC-C biology and their relationships with pathologies such as inflammatory bowel disease, colorectal cancer, and obesity can be leveraged to devise novel therapeutics.

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Section: Learning Opportunities and Prospectssupporting

confidence: 78%

Receptor Guanylyl Cyclase C and Cyclic GMP in Health and Disease: Perspectives and Therapeutic Opportunities

2022

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Impaired Intestinal Sodium Transport in Inflammatory Bowel Disease: From the Passenger to the Driver's Seat

Prasad

Visweswariah

2021

Cellular and Molecular Gastroenterology and Hepatology

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Mucosal potassium efflux mediated via Kcnn4 channels provides the driving force for electrogenic anion secretion in colon

Kumar¹,

Singh

Rajendran

2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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Intermediate conductance K(+) (Kcnn4) channels are present in both mucosal and serosal membranes of colon. However, only serosal Kcnn4 channels have been shown to be essential for agonist-induced (cAMP and Ca(2+)) anion secretion. The present study sought to determine whether mucosal Kcnn4 channels also play a role in colonic anion secretion. Mucosal-to-serosal and serosal-to-mucosal unidirectional (86)Rb (K(+) surrogate) fluxes as well as short-circuit current (I(sc); a measure of anion secretion) were measured under voltage-clamp conditions in distal colon from rats fed either a standard or K(+)-free diet. 5,6-Dichloro-1-ethyl-1,3-dihydro-2H-benzimidazole-2-one (DC-EBIO) was used to activate Kcnn4 channels. Mucosal DC-EBIO both induced K(+) secretion and enhanced anion secretion in normal rat distal colon. The DC-EBIO-induced K(+) secretion was completely blocked by nonspecific (Ba(2+)) and Kcnn4-specific (TRAM-34) inhibitors, but was not blocked by the large-conductance K(+) (iberiotoxin), small-conductance K(+) (apamin), or KCNQ1 (chromanol 293B) specific blockers. Ba(2+) and TRAM-34 also inhibited DC-EBIO-enhanced anion secretion. The DC-EBIO-enhanced anion secretion was completely inhibited by the nonspecific anion channel blocker 5-nitro-2-(3-phenylpropyl-amino)benzoic acid, whereas it was only partially inhibited by CFTR [CFTR(inh)-172, glibenclamide]- and CaCC (niflumic acid)-specific Cl(-) channel blockers. In contrast, mucosal DC-EBIO-enhanced K(+) and anion secretion was not present in distal colon of dietary K-depleted rats, indicating absence of mucosal Kcnn4 channels. These observations indicate that mucosal Kcnn4 channels are capable of driving agonist-induced anion secretion mediated via CFTR and CaCC and likely contribute to stool K(+) losses that accompany diarrheal illnesses.

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Cyclic Nucleotide Concentrations of Rectal Mucosa in Ulcerative Colitis

Cited by 3 publications

References 12 publications

Receptor Guanylyl Cyclase C and Cyclic GMP in Health and Disease: Perspectives and Therapeutic Opportunities

Receptor Guanylyl Cyclase C and Cyclic GMP in Health and Disease: Perspectives and Therapeutic Opportunities

Impaired Intestinal Sodium Transport in Inflammatory Bowel Disease: From the Passenger to the Driver's Seat

Mucosal potassium efflux mediated via Kcnn4 channels provides the driving force for electrogenic anion secretion in colon

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