ABSTRACT
BACKGROUND: Functional dyspepsia (FD) is one of the most common disorders of gastrointestinal (GI) diseases. However, no curable treatment is available for FD because the detailed mechanism of GI dysfunction in stressed conditions remains unclear. We aimed to clarify the association between endogenous acylated ghrelin signaling and gastric motor dysfunction and explore the possibility of a drug with ghrelin signal-enhancing action for FD treatment. METHODS: Solid gastric emptying (GE) and plasma acylated ghrelin levels were evaluated in an urocortin1 (UCN1) -induced stress model. To clarify the role of acylated ghrelin on GI dysfunction in the model, exogenous acylated ghrelin, an endogenous ghrelin enhancer, rikkunshito, or an α2 -adrenergic receptor (AR) antagonist was administered. Postprandial motor function was investigated using a strain gauge force transducer in a free-moving condition. KEY RESULTS: Exogenous acylated ghrelin supplementation restored UCN1-induced delayed GE. Alpha2 -AR antagonist and rikkunshito inhibited the reduction in plasma acylated ghrelin and GE in the stress model. The action of rikkunshito on delayed GE was blocked by co-administration of the ghrelin receptor antagonist. UCN1 decreased the amplitude of contraction in the antrum while increasing it in the duodenum. The motility index of the antrum but not the duodenum was significantly reduced by UCN1 treatment, which was improved by acylated ghrelin or rikkunshito. CONCLUSIONS & INFERENCES: The UCN1-induced gastric motility dysfunction was mediated by abnormal acylated ghrelin dynamics. Supplementation of exogenous acylated ghrelin or enhancement of endogenous acylated ghrelin secretion by rikkunshito may be effective in treating functional GI disorders.
Subject(s)
Drugs, Chinese Herbal/administration & dosage , Gastric Emptying/drug effects , Gastrointestinal Diseases/prevention & control , Ghrelin/administration & dosage , Stress, Psychological/complications , Adrenergic alpha-2 Receptor Antagonists/pharmacology , Animals , Gastrointestinal Diseases/complications , Ghrelin/blood , Male , Muscle Contraction/drug effects , Oligopeptides/pharmacology , Postprandial Period/drug effects , Rats , Rats, Sprague-Dawley , Receptors, Ghrelin/antagonists & inhibitors , Stress, Psychological/chemically induced , Urocortins , Yohimbine/pharmacologyABSTRACT
K(V)11.1 (HERG) channels contribute to membrane potential in a number of excitable cell types. We cloned a variant of K(V)11.1 from human jejunum containing a 171 bp deletion spanning exons 3 and 4. Expression of a full-length cDNA clone containing this deletion gave rise to protein that trafficked to the cell membrane and generated robust currents. The deletion occurred in a G/C-rich region and identical sequence elements of UGGUGG were located at the deletion boundaries. In recent studies these features have been implicated to cause deletions via template switching during cDNA synthesis. To examine this possibility we compared cDNAs from human brain, heart, and jejunum synthesized at lower (42 degrees C) and higher temperatures (70 degrees C). The 171 bp deletion was absent at the higher temperature. Our results suggest that the sequence and secondary structure of mRNA in the G/C rich region leads to template switching producing a cDNA product with a 171 bp deletion.
Subject(s)
Exons/genetics , Potassium Channels, Voltage-Gated/genetics , Transcription, Genetic/genetics , Amino Acid Sequence , Base Sequence , Brain/metabolism , Cell Line , DNA, Complementary/genetics , DNA, Complementary/metabolism , Gene Expression Profiling , Histidine/genetics , Histidine/immunology , Humans , Jejunum/metabolism , Membrane Potentials/genetics , Membrane Potentials/physiology , Microscopy, Confocal , Molecular Sequence Data , Myocardium/metabolism , Nucleic Acid Conformation , RNA/chemistry , RNA/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sequence Deletion , Temperature , Templates, Genetic , TransfectionABSTRACT
Growth of Streptomyces clavuligerus NP1 in the presence of methanol or ethanol resulted in a marked increase in production of cephalosporin(s) from penicillin G by resting cells. The mycelium produced in alcohol-supplemented medium was fragmented and dispersed as compared with growth in control medium. HPLC analysis showed that at least two products were present in the biotransformation supernatant fluid after 1 h incubation. One of them has been identified as deacetoxycephalosporin G (DAOG).
Subject(s)
Alcohols/pharmacology , Cephalosporins/metabolism , Penicillin G/metabolism , Penicillins/metabolism , Streptomyces/drug effects , Biotransformation/drug effects , Cephalosporins/analysis , Chromatography, High Pressure Liquid , Culture Media/chemistry , Ethanol/pharmacology , Methanol/pharmacology , Streptomyces/growth & development , Streptomyces/metabolism , Time FactorsABSTRACT
In the course of our screening program for acyl-CoA : cholesterol acyltransferase (ACAT) inhibitors from Korean herbal medicines, ACAT inhibitors were isolated from the hairy roots of Panax ginseng (Araliaceae) and identified as panaxynol, panaxydol, panaxydiol, and panaxytriol. These active compounds inhibit rat liver ACAT with IC50 values of 94, 80, 45 and 79 microM, respectively.