The multiple and enigmatic roles of guanylyl cyclase C in intestinal homeostasis

Arshad, Najla; Visweswariah, Sandhya S.

doi:10.1016/j.febslet.2012.07.028

Cited by 65 publications

(76 citation statements)

References 63 publications

(86 reference statements)

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“…Tissues were collected from Gulf toadfish kept in 33-35 ppt seawater for the tissue distribution study and from Gulf toadfish acclimated to 0 (control), 6,12,24, and 96 h in 60 ppt for the hypersalinity study. Collected tissues were homogenized with an Ultra-Turrax T8 homogenizer (Ika-Werke, Breisgau, Baden-Württem-berg, Germany) and 50 -100 mg/ml of total RNA was extracted with RNA STAT-60 (Tel-Test, Friendswood, TX).…”

Section: Rna Isolation and Molecular Cloningmentioning

confidence: 99%

“…These short-length hormones are expressed in the intestine and rectum of the Japanese eel, European eel (A. anguilla), and Gulf toadfish (41,47,48), and they are upstream regulators of apical guanylyl cyclase-C1 and -C2 (GC-C) receptors in the intestine (56). GC-C activation leads to increases in intracellular cGMP formation, whose downstream effects stimulate Cl Ϫ secretion by activation of the apical cystic fibrosis transmembrane conductance regulator (CFTR) and greatly inhibit ion and water absorption (3,4,6,40). In the Gulf toadfish and Japanese eel, the guanylin peptide effect appears restricted to the mid-and posterior intestine, by reversing the absorptive short-circuit current (I SC ) (from mucosa-to-serosa to serosa-tomucosa), mediated primarily by a switch from net Cl Ϫ absorpAddress for reprint requests and other correspondence: I. M. Ruhr,…”

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confidence: 99%

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The role of the rectum in osmoregulation and the potential effect of renoguanylin on SLC26a6 transport activity in the Gulf toadfish (Opsanus beta)

Ruhr

Takei

Grosell

2016

American Journal of Physiology-Regulatory, Integrative and Comp

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Ruhr IM, Takei Y, Grosell M. The role of the rectum in osmoregulation and the potential effect of renoguanylin on SLC26a6 transport activity in the Gulf toadfish (Opsanus beta). Am J Physiol Regul Integr Comp Physiol 311: R179 -R191, 2016. First published March 30, 2016 doi:10.1152/ajpregu.00033.2016.-Teleosts living in seawater continually absorb water across the intestine to compensate for branchial water loss to the environment. The present study reveals that the Gulf toadfish (Opsanus beta) rectum plays a comparable role to the posterior intestine in ion and water absorption. However, the posterior intestine appears to rely more on SLC26a6 (a HCO 3 Ϫ /Cl Ϫ antiporter) and the rectum appears to rely on NKCC2 (SLC12a1) for the purposes of solute-coupled water absorption. The present study also demonstrates that the rectum responds to renoguanylin (RGN), a member of the guanylin family of peptides that alters the normal osmoregulatory processes of the distal intestine, by inhibited water absorption. RGN decreases rectal water absorption more greatly than in the posterior intestine and leads to net Na ϩ and Cl Ϫ secretion, and a reversal of the absorptive short-circuit current (ISC). It is hypothesized that maintaining a larger fluid volume within the distal segments of intestinal tract facilitates the removal of CaCO3 precipitates and other solids from the intestine. Indeed, the expression of the components of the Cl Ϫ -secretory response, apical CFTR, and basolateral NKCC1 (SLC12a2), are upregulated in the rectum of the Gulf toadfish after 96 h in 60 ppt, an exposure that increases CaCO3 precipitate formation relative to 35 ppt. Moreover, the downstream intracellular effects of RGN appear to directly inhibit ion absorption by NKCC2 and anion exchange by SLC26a6. Overall, the present findings elucidate key electrophysiological differences between the posterior intestine and rectum of Gulf toadfish and the potent regulatory role renoguanylin plays in osmoregulation. water secretion; Cl Ϫ secretion; HCO 3 Ϫ secretion; intestine; marine teleost; CFTR SEAWATER TELEOST FISH LIVE IN an environment that is hypertonic to their blood plasma, resulting in continual water loss through the gills (34). To compensate for this, seawater teleosts drink copious volumes of water that are continually desalinated by the esophagus and gastrointestinal tract to produce a fluid that is roughly isotonic to blood plasma (17, 34). The constant absorption of ions, by the intestine, is critical as it lowers luminal osmolality and allows for solute-coupled water absorption, and, thereby, compensating for branchial water loss (45,46 (53), a process coupled to the ion transport mechanisms described above. The seawater teleost rectum also plays a role in water absorption. For instance, in the sea bream (Sparus aurata) and Japanese eel (Anguilla japonica), fluid absorption by the rectum also occurs via aquaporins, but the rate of absorption is less than in the intestine (8,15,28,36). The rectum of the Gulf toadfish (Opsanus beta) also expres...

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Section: Rna Isolation and Molecular Cloningmentioning

confidence: 99%

mentioning

confidence: 99%

The role of the rectum in osmoregulation and the potential effect of renoguanylin on SLC26a6 transport activity in the Gulf toadfish (Opsanus beta)

Ruhr

Takei

Grosell

2016

American Journal of Physiology-Regulatory, Integrative and Comp

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“…*Differences from the control within a tissue; †transepithelial conductance (Gte) value of the anterior intestine at any given dose is significantly greater than its counterpart value in the posterior intestine (P Ͻ 0.05). intestine (4). Nonetheless, stimulation of fish and mammalian GC-Cs expressed in cell culture lines by GN or UGN leads to significant guanylyl cyclase activity and increases in cGMP (10,13,15,36,53,69), yet, in the anterior intestine of marine teleosts, these increases may not be occurring in significant amounts (if at all) to produce the downstream effects observed in the posterior intestine.…”

Section: Tissue-specific Responses To Eel Gn Ugn and Rgnmentioning

confidence: 99%

“…GN and UGN bind to guanylyl cyclase-C (GC-C), a transmembrane receptor on the apical membrane of intestinal tissues (50,52,53), causing an intracellular transduction cascade that increases the formation of cyclic guanosine monophosphate (cGMP). cGMP can either stimulate cGMP-dependent protein kinase (PKG) or lead to increases in cyclic adenosine monophosphate (cAMP) levels that stimulate cAMP-dependent protein kinase (PKA); both PKG and PKA activate CFTR (3,4,9,13,34,42). In mammals, this leads to Cl Ϫ , fluid, and HCO 3 Ϫ secretion into the intestinal lumen to help neutralize the effects of acidic chyme (2,5,30,54).…”

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confidence: 99%

Guanylin peptides regulate electrolyte and fluid transport in the Gulf toadfish (Opsanus beta) posterior intestine

Ruhr

Bodinier

Mager

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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The physiological effects of guanylin (GN) and uroguanylin (UGN) on fluid and electrolyte transport in the teleost fish intestine have yet to be thoroughly investigated. In the present study, the effects of GN, UGN, and renoguanylin (RGN; a GN and UGN homolog) on short-circuit current ( Isc) and the transport of Cl−, Na+, bicarbonate (HCO3−), and fluid in the Gulf toadfish ( Opsanus beta) intestine were determined using Ussing chambers, pH-stat titration, and intestinal sac experiments. GN, UGN, and RGN reversed the Isc of the posterior intestine (absorptive-to-secretory), but not of the anterior intestine. RGN decreased baseline HCO3− secretion, but increased Cl− and fluid secretion in the posterior intestine. The secretory response of the posterior intestine coincides with the presence of basolateral NKCC1 and apical cystic fibrosis transmembrane conductance regulator (CFTR), the latter of which is lacking in the anterior intestine and is not permeable to HCO3− in the posterior intestine. However, the response to RGN by the posterior intestine is counterintuitive given the known role of the marine teleost intestine as a salt- and water-absorbing organ. These data demonstrate that marine teleosts possess a tissue-specific secretory response, apparently associated with seawater adaptation, the exact role of which remains to be determined.

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“…Both pro-UGN and UGN activate the guanilate cyclase 2C receptor (GUCY2C), which is also targeted by diarrheagenic bacterial heat-stable enterotoxins (STs) (6). The activation of GUCY2C leads to elevated intracellular levels of cyclic guanosine monophosphate (7), which in invertebrate species has been demonstrated to lead to alterations in food behavior and energy-balance regulation (8,9). Circulating UGN levels were decreased in fasted and leptin-deficient mice but recovered after refeeding or exogenous leptin infusion (10), suggesting that UGN is regulated by nutritional status in a leptin-dependent manner.…”

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confidence: 99%

Uroguanylin Action in the Brain Reduces Weight Gain in Obese Mice via Different Efferent Autonomic Pathways

et al. 2015

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The gut-brain axis is of great importance in the control of energy homeostasis. The identification of uroguanylin (UGN), a peptide released in the intestines that is regulated by nutritional status and anorectic actions, as the endogenous ligand for the guanylyl cyclase 2C receptor has revealed a new system in the regulation of energy balance. We show that chronic central infusion of UGN reduces weight gain and adiposity in diet-induced obese mice. These effects were independent of food intake and involved specific efferent autonomic pathways. On one hand, brain UGN induces brown adipose tissue thermogenesis, as well as browning and lipid mobilization in white adipose tissue through stimulation of the sympathetic nervous system. On the other hand, brain UGN augments fecal output through the vagus nerve. These findings are of relevance as they suggest that the beneficial metabolic actions of UGN through the sympathetic nervous system do not involve nondesirable gastrointestinal adverse effects, such as diarrhea. The present work provides mechanistic insights into how UGN influences energy homeostasis and suggests that UGN action in the brain represents a feasible pharmacological target in the treatment of obesity.After the ingestion of a meal, the presence of nutrients in the gastrointestinal (GI) tract initiates complex neural and hormonal responses that send signals to the brain about the ongoing changes in nutritional status. Among the different strategies used to communicate to the brain, the gut secretes peptides that reach the central nervous system (CNS) via afferent nerve fibers or the circulation (1,2). New gut hormones are continuously discovered, and, with the exception of ghrelin, which is the only peptidic hormone favoring weight gain and adiposity, all of them are associated with a negative energy balance and are thus potential targets for the treatment of obesity (3,4).One of the most recently discovered gut hormones is uroguanylin (UGN), a 16-amino acid peptide secreted mainly from duodenal epithelial cells. UGN is synthesized as a prohormone (pro-UGN), which, after cleavage by a still unknown enzyme, is converted to the active UGN (3,5). Both pro-UGN and UGN activate the guanilate cyclase 2C receptor (GUCY2C), which is also targeted by diarrheagenic bacterial heat-stable enterotoxins (STs) (6). The activation of GUCY2C leads to elevated intracellular levels of cyclic guanosine monophosphate (7), which in invertebrate species has been demonstrated to lead to alterations in food behavior and energy-balance regulation (8,9). Circulating UGN levels were decreased in fasted and leptin-deficient mice but recovered after refeeding or exogenous leptin

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The multiple and enigmatic roles of guanylyl cyclase C in intestinal homeostasis

Cited by 65 publications

References 63 publications

The role of the rectum in osmoregulation and the potential effect of renoguanylin on SLC26a6 transport activity in the Gulf toadfish (Opsanus beta)

The role of the rectum in osmoregulation and the potential effect of renoguanylin on SLC26a6 transport activity in the Gulf toadfish (Opsanus beta)

Guanylin peptides regulate electrolyte and fluid transport in the Gulf toadfish (Opsanus beta) posterior intestine

Uroguanylin Action in the Brain Reduces Weight Gain in Obese Mice via Different Efferent Autonomic Pathways

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