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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-2-21
pubmed:abstractText
Four linear beta(2)/beta(3)-di- and alpha/beta(3)-tetrapeptides (1-4) were investigated as somatostatin sst(4) receptor agonists on recombinant human and mouse somatostatin receptors. Human somatostatin receptor subtypes 1-5 (sst(1-5)), and mouse somatostatin receptor subtypes 1,3,4 and 5, were characterised using the agonist radioligands [(125)I]LTT-SRIF-28, [(125)I][Tyr(10)]CST(14) and [(125)I]CGP 23996 in stably transfected Chinese hamster lung fibroblast (CCL39) cells. The peptides bound selectively to sst(4) receptors with nanomolar affinity (pK(d)=5.4-7.8). The peptides were investigated on second messenger systems both as agonists, and as antagonists to SRIF-14-mediated effects in CCL39 cells expressing mouse sst(4 )receptors, via measurement of inhibition of forskolin-stimulated adenylate cyclase activity, and stimulation of luciferase expression. The peptides showed full agonism or pronounced partial agonism (40 to 100% relative intrinsic activity) in both inhibition of forskolin-stimulated adenylate cyclase activity (pEC(50)=5.5-6.8), and luciferase expression (pEC(50)=5.5-6.5). The agonist potential was confirmed since antagonism was very difficult to establish. The data show that beta(2)/beta(3)-di- and alpha/beta(3)-tetrapeptide derivatives have agonist potential at recombinant somatostatin sst(4) receptors. Therefore, they may be used to elucidate physiological and biochemical effects mediated by sst(4), and may also have potential as therapeutic agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0028-1298
pubmed:author
pubmed:issnType
Print
pubmed:volume
367
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
95-103
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12595949-Adenylate Cyclase, pubmed-meshheading:12595949-Animals, pubmed-meshheading:12595949-Cells, Cultured, pubmed-meshheading:12595949-Cricetinae, pubmed-meshheading:12595949-Cricetulus, pubmed-meshheading:12595949-Dipeptides, pubmed-meshheading:12595949-Enzyme Inhibitors, pubmed-meshheading:12595949-Fibroblasts, pubmed-meshheading:12595949-Forskolin, pubmed-meshheading:12595949-Humans, pubmed-meshheading:12595949-Ligands, pubmed-meshheading:12595949-Luciferases, pubmed-meshheading:12595949-Lung, pubmed-meshheading:12595949-Membrane Proteins, pubmed-meshheading:12595949-Mice, pubmed-meshheading:12595949-Oligopeptides, pubmed-meshheading:12595949-Radioligand Assay, pubmed-meshheading:12595949-Receptors, Somatostatin, pubmed-meshheading:12595949-Structure-Activity Relationship
pubmed:year
2003
pubmed:articleTitle
Beta(2)/beta(3)-di- and alpha/beta(3)-tetrapeptide derivatives as potent agonists at somatostatin sst(4) receptors.
pubmed:affiliation
Nervous System Research, WSJ 386/745, Novartis Pharma AG, 4002, Basel, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't