Linked Life Data

11162621

Source:http://linkedlifedata.com/resource/pubmed/id/11162621

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-2-22
pubmed:abstractText
Orexin-A is a neuropeptide consisting of 33 amino acids with two intrachain disulfide bonds, namely Cys6-Cys12 and Cys7-Cys14, and is a potent stimulator of food consumption and gastric acid secretion. In contrast, orexin-B, a peptide containing 28 amino acids without disulfide bond, which has no stimulatory action of gastric acid. The objective of the present study was to characterize the receptor-mediated mechanism of orexin-A-induced stimulation of gastric acid secretion using orexin-A-related peptides with modification of disulfide bonds. Intracisternal injection of orexin-A, but not orexin-B or orexin-A (15-33), that does not contain both disulfide bonds stimulated gastric acid secretion in pylorus-ligated conscious rats. The ability of the stimulation of gastric acid output was less in three alanine-substituted orexin-A, [Ala(6,12)]orexin-A, [Ala(7,14)]orexin-A, and [Ala(6,7,12,14)]orexin-A, than orexin-A. Orexins-induced calcium increase was measured in CHO-K1 cells expressing OX1R or OX2R. Orexin-A induced a transient increase in [Ca(2+)]i in CHO-K1/OX1R cells in a dose-dependent manner. EC50 values for OX1R of orexin-A, orexin-B, or orexin-A (15-33) was 0.068, 0.69 or 4.1 nM, respectively, suggesting that peptides containing no disulfide bonds have lower potency for the receptor. Agonistic activity for OX1R of the three orexin-A analogues with modification of one or both disulfide bonds was significantly reduced as compared with that of orexin-A. EC50 values for OX2R of orexin-A and orexin-B was almost equal but potency for the receptor of orexin-A (15-33) and three alanine substituted orexin-A was less than that of orexin-A. A significant inverse relationship between gastric acid output and EC50 values for OX1R, but not OX2R, was observed. These results suggested that the orexin-A-induced acid stimulation requires OX1R activation and that disulfide bonds in orexin-A may have a key role in the receptor activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-291X
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Academic Press.
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
976-81
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11162621-Amino Acid Sequence, pubmed-meshheading:11162621-Animals, pubmed-meshheading:11162621-CHO Cells, pubmed-meshheading:11162621-Calcium, pubmed-meshheading:11162621-Carrier Proteins, pubmed-meshheading:11162621-Cattle, pubmed-meshheading:11162621-Cricetinae, pubmed-meshheading:11162621-Disulfides, pubmed-meshheading:11162621-Dose-Response Relationship, Drug, pubmed-meshheading:11162621-Gastric Acid, pubmed-meshheading:11162621-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:11162621-Kinetics, pubmed-meshheading:11162621-Ligands, pubmed-meshheading:11162621-Male, pubmed-meshheading:11162621-Mice, pubmed-meshheading:11162621-Molecular Sequence Data, pubmed-meshheading:11162621-Neuropeptides, pubmed-meshheading:11162621-Rats, pubmed-meshheading:11162621-Rats, Sprague-Dawley, pubmed-meshheading:11162621-Receptors, G-Protein-Coupled, pubmed-meshheading:11162621-Receptors, Neuropeptide
pubmed:year
2001
pubmed:articleTitle
Requirement of intact disulfide bonds in orexin-A-induced stimulation of gastric acid secretion that is mediated by OX1 receptor activation.
pubmed:affiliation
Third Department of Internal Medicine, Asahikawa Medical College, Asahikawa, Japan. okumurat@asahikawa-med.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't