Linked Life Data

18607779

Source:http://linkedlifedata.com/resource/pubmed/id/18607779

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2008-11-26
pubmed:abstractText
The effects of pituitary adenylate cyclase activating polypeptide (PACAP) are mediated through G-protein-coupled receptors, the specific PAC1 receptor and VPAC1 and VPAC2 receptors which bind vasoactive intestinal peptide with similar affinity. Based on binding affinity studies, PACAP6-38 was discovered as a potent antagonist of PAC1 and it has been used by hundreds of studies as a PACAP antagonist. Recently, we have found that in certain cells/tissues, PACAP6-38 does not antagonize PACAP-induced effects, but surprisingly, it exerts similar actions to PACAP1-38, behaving as an agonist. In the present study, we report on the agonistic behavior of PACAP6-38 on neuropeptide release from sensory nerves of the isolated rat trachea and on the MAPK signaling pathways in cytotrophoblast cells. In isolated rat tracheae, PACAP6-38, similarly to PACAP1-38, induced significant inhibitory effects on the release of three simultaneously measured sensory neuropeptides, substance P, calcitonin gene-related peptide, and somatostatin evoked by both chemical excitation and electrical field stimulation of capsaicin-sensitive afferents. Effects of PACAP6-38 were the same as those of PACAP1-38 on MAPK signaling in human cytotrophoblast cells. Western blot analysis showed that both peptide forms stimulated ERK1/2 and JNK phosphorylation, while they both inhibited p38 MAPK phosphorylation. The most pronounced effects were observed when both peptides were present. In summary, our results show that PACAP6-38, which is a PACAP receptor antagonist in most cells/tissues, can behave as an agonist in other systems. The increasing interest in the effects of PACAP requires further studies on the pharmacological properties of the peptide and its analogues.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0895-8696
pubmed:author
pubmed:issnType
Print
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
270-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18607779-Animals, pubmed-meshheading:18607779-Calcitonin Gene-Related Peptide, pubmed-meshheading:18607779-Capsaicin, pubmed-meshheading:18607779-Cell Line, Tumor, pubmed-meshheading:18607779-Humans, pubmed-meshheading:18607779-MAP Kinase Signaling System, pubmed-meshheading:18607779-Male, pubmed-meshheading:18607779-Mitogen-Activated Protein Kinases, pubmed-meshheading:18607779-Peptide Fragments, pubmed-meshheading:18607779-Pituitary Adenylate Cyclase-Activating Polypeptide, pubmed-meshheading:18607779-Rats, pubmed-meshheading:18607779-Rats, Wistar, pubmed-meshheading:18607779-Sensory Receptor Cells, pubmed-meshheading:18607779-Sensory System Agents, pubmed-meshheading:18607779-Somatostatin, pubmed-meshheading:18607779-Substance P, pubmed-meshheading:18607779-Tissue Culture Techniques, pubmed-meshheading:18607779-Trachea, pubmed-meshheading:18607779-Trophoblasts
pubmed:year
2008
pubmed:articleTitle
Agonistic behavior of PACAP6-38 on sensory nerve terminals and cytotrophoblast cells.
pubmed:affiliation
Department of Anatomy, University of Pecs, Pecs, Hungary.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't