Linked Life Data

1327769

Source:http://linkedlifedata.com/resource/pubmed/id/1327769

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1992-10-26
pubmed:abstractText
N-terminally shortened analogs of the 27-amino-acid and 38-amino-acid forms of the pituitary-adenylate-cyclase-activating neuropeptide, PACAP(1-27) and PACAP(1-38), were synthesized by a solid-phase method. Systematic deletion of the first 13 amino acids of both PACAP was tested by evaluating their ability to occupy the specific and selective PACAP receptor of human neuroblastoma NB-OK-1 cell membranes and to stimulate adenylate cyclase or, when inactive per se, to inhibit PACAP-stimulated adenylate cyclase activity. For each peptide, the Kact (concentration required for half-maximal adenylate cyclase activation) or Ki [concentration required to shift the dose/response curve of PACAP(1-27) twofold to the right] was in good agreement with the corresponding IC50 [concentration inhibiting 50% of 125I-[AcHis1]PACAP(1-27) binding to membranes], suggesting interaction with the same homogeneous class of adenylate cyclase-coupled receptors. The deletion of the two first amino acids (His1 and Ser2) sufficed to decrease the affinity for receptors and to suppress the capacity to activate adenylate cyclase. The shorter fragments 3-27 and 3-38, 4-27 and 4-38, 5-27 and 5-38, 6-27 and 6-38, 7-27 and 7-38, 8-27 and 8-38, and 9-27 and 9-38 were all competitive antagonists of PACAP(1-27)-stimulated activity with the N-terminally shortened PACAP(1-38) derivatives being 4-30-fold more potent than the equivalent PACAP(1-27) derivatives. In this group PACAP(6-38) was the most potent antagonist (Ki 1.5 nM). Surprisingly, the N-terminally shorter fragments 10-27 and 10-38, 11-27 and 11-38, 12-27 and 12-38, 13-27 and 13-38, and 14-27 and 14-38 were again able to stimulate adenylate cyclase, the smallest fragments, PACAP(14-27) and PACAP(14-38), being the most potent and efficient (Kact 2 microM and 0.1 microM, respectively). In this group of agonists, PACAP(1-38) derivatives deleted at the N-terminus were also more potent than the equivalent PACAP(1-27) derivatives.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0014-2956
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
208
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
815-9
pubmed:dateRevised
2007-7-23
pubmed:meshHeading
pubmed-meshheading:1327769-Adenylate Cyclase, pubmed-meshheading:1327769-Amino Acid Sequence, pubmed-meshheading:1327769-Binding, Competitive, pubmed-meshheading:1327769-Cell Membrane, pubmed-meshheading:1327769-Enzyme Activation, pubmed-meshheading:1327769-Humans, pubmed-meshheading:1327769-Molecular Sequence Data, pubmed-meshheading:1327769-Neuroblastoma, pubmed-meshheading:1327769-Neuropeptides, pubmed-meshheading:1327769-Pituitary Adenylate Cyclase-Activating Polypeptide, pubmed-meshheading:1327769-Pituitary Gland, pubmed-meshheading:1327769-Receptors, Cell Surface, pubmed-meshheading:1327769-Receptors, Pituitary Adenylate Cyclase-Activating..., pubmed-meshheading:1327769-Receptors, Pituitary Hormone, pubmed-meshheading:1327769-Signal Transduction, pubmed-meshheading:1327769-Structure-Activity Relationship, pubmed-meshheading:1327769-Tumor Cells, Cultured
pubmed:year
1992
pubmed:articleTitle
Antagonistic properties are shifted back to agonistic properties by further N-terminal shortening of pituitary adenylate-cyclase-activating peptides in human neuroblastoma NB-OK-1 cell membranes.
pubmed:affiliation
Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Belgium.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't