K+ secretion activated by luminal P2Y2 and P2Y4 receptors in mouse colon

Matos, Joana; Robaye, Bernard; Boeynaems, Jean‐Marie; Beauwens, Renaud; Leipziger, Jens

doi:10.1113/jphysiol.2004.080002

Cited by 80 publications

(85 citation statements)

References 37 publications

(54 reference statements)

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“…We therefore considered the BK channel as the first-choice candidate. This also was suggested in a previous work that showed that luminal iberiotoxin, a specific blocker for BK (large conductance) channels, was able to inhibit strongly the luminal nucleotide-triggered K ϩ secretion (5 …”

Section: N Patients With Esrd Fecal Kmentioning

confidence: 49%

“…Luminal UTP stimulates a rapid and transient deflection of V te to lumenpositive values in WT mice. As described previously, this phenomenon was inhibited greatly by luminal Ba 2ϩ and luminal IBTx and thus was identified as K ϩ secretion in distal colon (4,5). In contrast, luminal UTP does not promote K ϩ secretion in BK Ϫ/Ϫ mice.…”

Section: Statistical Analysesmentioning

confidence: 69%

“…In distal colonic epithelium, the relevant K ϩ channel in the luminal membrane remains to be established. For this purpose, we exploit the physiologic phenomenon that luminal nucleotide P2Y receptors in rat and mouse colon stimulate an electrogenic K ϩ secretory burst (4,5). This transient K ϩ secretion may be involved in a local intrinsic epithelial reflex that use-dependently becomes active during the stool passage.…”

Section: N Patients With Esrd Fecal Kmentioning

confidence: 99%

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Distal Colonic K+ Secretion Occurs via BK Channels

Sausbier¹,

Matos²,

Sausbier³

et al. 2006

Journal of the American Society of Nephrology

108

125

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K؉ secretion in the kidney and distal colon is a main determinant of K ؉ homeostasis. This study investigated the identity of the relevant luminal secretory K ؉ ion channel in distal colon. An Ussing chamber was used to measure ion transport in the recently generated BK channel-deficient (BK ؊ -activated K ϩ channel, i.e., of small, intermediate, or large conductance (9,10). In some epithelia, including rodent colon, evidence indicates that BK channels (large conductance) localize to the luminal membrane (11,12). We therefore considered the BK channel as the first-choice candidate. This also was suggested in a previous work that showed that luminal iberiotoxin, a specific blocker for BK (large conductance) channels, was able to inhibit strongly the luminal nucleotide-triggered K / Materials and Methods MiceThe previously generated BK Ϫ/Ϫ and wild-type (WT) littermate mice on hybrid 129Sv/C57BL6 background were used (F2 generation) (13). Generation of SK4 channel-deficient (SK4 Ϫ/Ϫ ) mice was as follows:Using a genomic 129/ola cosmid library (RZPD), the targeting vector was constructed such that the pore exon was flanked by a single loxP site and a floxed neo/tk cassette. This construct was electroporated into R1 embryonic stem (ES) cells, and G418-resistant clones were screened. Two positive clones, analyzed by Southern blotting, were transiently transfected with a Cre-expressing plasmid to excise the neo/tk cassette and the pore exon yielding L1/ϩ clones. Correctly targeted L1/ϩ clones were

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Section: N Patients With Esrd Fecal Kmentioning

confidence: 49%

Section: Statistical Analysesmentioning

confidence: 69%

Section: N Patients With Esrd Fecal Kmentioning

confidence: 99%

See 1 more Smart Citation

Distal Colonic K+ Secretion Occurs via BK Channels

Sausbier¹,

Matos²,

Sausbier³

et al. 2006

Journal of the American Society of Nephrology

108

125

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“…P2Y 2 and P2Y 4 receptors are very prevalent luminal receptors involved in Cl -, HCO 3 -, K + secretion, or mucin secretion. Nucleotide stimulation of K + secretion occurs in the distal colon, K + secretion and HCO 3 -secretion in the gallbladder (Table 3; [17,18,75,90]); HCO 3 -secretion also occurs in ducts and is involved in the formation of pancreatic juice. Stimulation of Cl -secretion occurs in the gallbladder, small intestine, and duct cells.…”

Section: Enac and Cftr Channelsmentioning

confidence: 99%

Purinergic receptors and gastrointestinal secretomotor function

Christofi

2008

Purinergic Signalling

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Secretomotor reflexes in the gastrointestinal (GI) tract are important in the lubrication and movement of digested products, absorption of nutrients, or the diarrhea that occurs in diseases to flush out unwanted microbes. Mechanical or chemical stimulation of mucosal sensory enterochromaffin (EC) cells triggers release of serotonin (5-HT) (among other mediators) and initiates local reflexes by activating intrinsic primary afferent neurons of the submucous plexus. Signals are conveyed to interneurons or secretomotor neurons to stimulate chloride and fluid secretion. Inputs from myenteric neurons modulate secretory rates and reflexes, and special neural circuits exist to coordinate secretion with motility. Cellular components of secretomotor reflexes variably express purinergic receptors for adenosine (A1, A2a, A2b, or A3 receptors) or the nucleotides adenosine 5′-triphosphate (ATP), adenosine diphosphate (ADP), uridine 5′-triphosphate (UTP), or uridine diphosphate (UDP) (P2X 1-7 , P2Y 2 , P2Y 4 , P2Y 6 , P2Y 12 receptors). This review focuses on the emerging concepts in our understanding of purinergic regulation at these receptors, and in particular of mechanosensory reflexes. Purinergic inhibitory (A 1 , A 3 , P2Y 12 ) or excitatory (A 2 , P2Y 1 ) receptors modulate mechanosensitive 5-HT release. Excitatory (P2Y 1 , other P2Y, P2X) or inhibitory (A 1 , A 3 ) receptors are involved in mechanically evoked secretory reflexes or "neurogenic diarrhea." Distinct neural (pre-or postsynaptic) and non-neural distribution profiles of P2X 2 , P2X 3 , P2X 5 , P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 , or P2Y 12 receptors, and for some their effects on neurotransmission, suggests their role in GI secretomotor function. Luminal A 2b , P2Y 2 , P2Y 4 , and P2Y 6 receptors are involved in fluid and Cl -, HCO 3 -, K + , or mucin secretion. Abnormal receptor expression in GI diseases may be of clinical relevance. Adenosine A 2a or A 3 receptors are emerging as therapeutic targets in inflammatory bowel diseases (IBD) and gastroprotection; they can also prevent purinergic receptor abnormalities and diarrhea. Purines are emerging as fundamental regulators of enteric secretomotor reflexes in health and disease.

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“…Furthermore, a variety of experimental approaches have provided evidence that local ATP release and P2RY2 stimulation may inhibit water reabsorption in the collecting duct. 8 Previous studies in mice have identified important functions for P2RY2 in a variety of processes, including nucleotide-regulated Ca 2 þ signalling in lung fibroblasts and airway epithelial cells, 9 nucleotide-stimulated Cl À secretion in the trachea and gallbladder, 10 neuronal growth, 11 stimulation of K þ secretion in the colon 12 and neutrophil chemotaxis. 13 In 2007, Rieg et al 14 reported that saltresistant hypertension occurs in the P2Y2 receptor (mice homologue of the human P2RY2 gene) knockout mice because the baroreceptor response to variations in salt intake remains intact.…”

Section: Introductionmentioning

confidence: 99%

The purinergic receptor P2Y, G-protein coupled, 2 (P2RY2) gene associated with essential hypertension in Japanese men

et al. 2009

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P2RY2 has an important function in the regulation of blood pressure by activating adenosine triphosphate (ATP). The aim of this study was to investigate the association between the human P2RY2 gene and essential hypertension (EH) through a haplotype-based casecontrol study that included two gender groups. The 273 EH patients and 255 age-matched controls were genotyped for five single-nucleotide polymorphisms (SNPs) of the human P2RY2 gene (rs4944831, rs1783596, rs4944832, rs4382936 and rs10898909). Data were analysed for men and women separately and then as a combined total group. For the total and the men only groups, the genotype distribution of the T allele of rs4944831 and the recessive model (GG vs TG þ TT) of rs4944831 differed significantly between the EH patients and controls (P ¼ 0.028 and 0.019; P ¼ 0.009 and 0.008, respectively). Logistic regression showed that for the total and men groups, the TG þ TT genotype of rs4944831 was more prevalent in EH patients than in the controls (P ¼ 0.026 and 0.011, respectively). For men, the overall distribution of the haplotype (SNP2-SNP4-SNP5) was significantly different between the EH patients and the controls (P ¼ 0.006). As compared with controls, the frequency of the T-A-G haplotype was significantly higher, whereas the T-C-G haplotype was significantly lower for the EH patients (P ¼ 0.001 and 0.014, respectively). In conclusion, the present results indicate that rs4944831 and the T-A-G haplotype of the human P2RY2 gene might be genetic markers for EH in Japanese men.

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K⁺ secretion activated by luminal P2Y₂ and P2Y₄ receptors in mouse colon

Cited by 80 publications

References 37 publications

Distal Colonic K+ Secretion Occurs via BK Channels

Distal Colonic K+ Secretion Occurs via BK Channels

Purinergic receptors and gastrointestinal secretomotor function

The purinergic receptor P2Y, G-protein coupled, 2 (P2RY2) gene associated with essential hypertension in Japanese men

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