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Mechanical activation of the mucosal lining of the colon by brush stroking elicits an intestinal neural reflex and an increase in short circuit current (Isc) indicative of electrogenic chloride ion transport. We tested whether endogenous nucleotides are physiologic regulators of mucosal reflexes that control ion transport. The brush stroking-evoked Isc(More)
Nucleotides such as ATP and UTP are everywhere. They play a key role in transducing mechanosensory signals via P2Y receptors in the large intestine or colon, leading to secretion of the sensory mediator 5-HT, and act as autocrine, paracrine, or neurocrine mediators in neural reflexes regulating chloride secretion.
Stroking the mucosal lining of the guinea pig colon with a brush elicits an intestinal neural reflex, and an increase in short-circuit current (Isc) indicative of chloride secretion. We tested whether endogenous and exogenous nucleotides are physiologic regulators of mucosal reflexes that modulate chloride secretion. The basal Isc was augmented by(More)
BACKGROUND & AIMS The aim was to determine whether adenosine receptors modulate cAMP, intracellular free calcium ([Ca(2+)](i)), and 5-hydroxytryptamine (5-HT) release in human carcinoid BON cells. METHODS Adenosine receptor (R) mRNA, proteins, and function were identified by Western blots, immunofluorescent labeling, Fluo-4/AM [Ca(2+)](i) imaging, and(More)
Adenosine A3 receptors (ADOA3Rs) are emerging as novel purinergic targets for treatment of inflammatory diseases. Our goal was to assess the protective effect of the ADOA3R agonist N(6)-(3-iodobenzyl)-adenosine-5-N-methyluronamide (IB-MECA) on gene dysregulation and injury in a rat chronic model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)--induced(More)
BACKGROUND Expression of purine genes is modulated by inflammation or experimental colitis and altered expression leads to disrupted gut function. We studied purine gene dysregulation profiles in inflammatory bowel disease (IBD) and determined whether they can distinguish between Crohn's disease (CD) and ulcerative colitis (UC) using Pathway Analysis and a(More)
RATIONALE The role of purinergic signaling in human ENS is not well understood. We sought to further characterize the neuropharmacology of purinergic receptors in human ENS and test the hypothesis that endogenous purines are critical regulators of neurotransmission. EXPERIMENTAL APPROACH LSCM-Fluo-4/(Ca(2+))-imaging of postsynaptic Ca(2+) transients(More)
We tested the novel hypothesis that endogenous adenosine (eADO) activates low-affinity A3 receptors in a model of neurogenic diarrhea in the guinea pig colon. Dimaprit activation of H2 receptors was used to trigger a cyclic coordinated response of contraction and Cl(-) secretion. Contraction-relaxation was monitored by sonomicrometry (via intracrystal(More)
BACKGROUND Alterations in 5-hydroxytryptamine (HT) signaling in inflamed gut may contribute to pathogenesis of inflammatory bowel diseases. Adenosine 5'-triphosphate (ATP) regulates mucosal-mechanosensory reflexes and ATP receptors are sensitive to mucosal inflammation. Yet, it remains unknown whether ATP can modulate 5-HT signaling in enterochromaffin(More)
BACKGROUND Pharmacological studies suggest that adenosine A₃AR influences motility and colitis. Functional A₃⁻/⁻AR knockout mice were used to prove whether A₃AR activation is involved in modulating either motility or colitis. METHODS A₃AR was probed by polymerase chain reaction (PCR) genotyping, Western blot, and immunochemistry. Motility was assessed in(More)