Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021831 (enteropathy)
 4,403 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism by which excess quantities of bile salts in the colon produce diarrhea is not known. Therefore, experiments were performed in which the effect of conjugated dihydroxy bile salts on ion transport was evaluated in the in vitro short-circuited rat colon. 2 mM glycochenodeoxycholic acid (GCDC), taurochenodeoxycholic acid (TCDC), or taurodeoxycholic acid caused a prompt increase in short-circuit current (I(sc)) and electrical potential difference (PD). Similar results were obtained when theophylline was added. Removal of HCO(2) and C1 prevented the effects of both bile salts and theophylline. Pretreatment with theophylline blocked the increase in I(sc) and PD produced by TCDC and pretreatment with either TCDC or GCDC inhibited the expected theophylline response. Na fluxes in the presence of both TCDC and theophylline demonstrated a decrease in net absorption; and TCDC decreased net C1 absorption and theophylline caused a reversal of net C1 absorption to net C1 secretion. It is proposed that the diarrhea associated with cholerheic enteropathy is produced by active anion secretion possibly mediated by cyclic AMP.
 ...
PMID:Effect of conjugated dihydroxy bile salts on electrolyte transport in rat colon. 434 49

Celiac disease is an autoimmune enteropathy caused by a permanent intolerance to gliadins. In this study the effects of two gliadin-derived peptides (PA2, PQPQLPYPQPQLP and PA9, QLQPFPQPQLPY) on TNFalpha production by intestinal epithelial cells (Caco-2) and whether these effects were related to protein kinase A (PKA) and/or -C (PKC) activities have been evaluated. Caco-2 cell cultures were challenged with several sets of gliadin peptides solutions (0.25 mg/mL), with/without different activators of PKA or PKC, bradykinin (Brdkn) and pyrrolidine dithiocarbamate (PDTC). The gliadin-derived peptides assayed represent the two major immunodominant epitopes of the peptide 33-mer of alpha-gliadin (56-88) (LQLQPFPQPQLPYPQPQLPYPQPQLPYPQPQPF). Both peptides induced the TNFalpha production triggering the inflammatory cell responses, the PA2 being more effective. The addition of the peptides in the presence of dibutyril cyclic AMP (cAMP), Brdkn or PDTC, inhibited the TNFalpha production. The PKC-activator phorbol 12-myristate 13-diacetate additionally increased the PA2- and PA9-induced TNFalpha production. These results link the gliadin-derived peptides induced TNFalpha production through cAMP-dependent PKA activation, where ion channels controlling calcium influx into cells could play a protective role, and requires NF-kappaB activation.
 ...
PMID:Gliadins induce TNFalpha production through cAMP-dependent protein kinase A activation in intestinal cells (Caco-2). 2051 34

The intestine is the primary site of nutrient absorption, fluid-ion secretion, and home to trillions of symbiotic microbiota. The high turnover of the intestinal epithelia also renders it susceptible to neoplastic growth. These diverse processes are carefully regulated by an intricate signaling network. Among the myriad molecules involved in intestinal epithelial cell homeostasis are the second messengers, cyclic AMP (cAMP) and cyclic GMP (cGMP). These cyclic nucleotides are synthesized by nucleotidyl cyclases whose activities are regulated by extrinsic and intrinsic cues. Downstream effectors of cAMP and cGMP include protein kinases, cyclic nucleotide gated ion channels, and transcription factors, which modulate key processes such as ion-balance, immune response, and cell proliferation. The web of interaction involving the major signaling pathways of cAMP and cGMP in the intestinal epithelial cell, and possible cross-talk among the pathways, are highlighted in this review. Deregulation of these pathways occurs during infection by pathogens, intestinal inflammation, and cancer. Thus, an appreciation of the importance of cyclic nucleotide signaling in the intestine furthers our understanding of bowel disease, thereby aiding in the development of therapeutic approaches.
 ...
PMID:Cyclic nucleotide signaling in intestinal epithelia: getting to the gut of the matter. 2361 87