Linked Life Data

10414962

Source:http://linkedlifedata.com/resource/pubmed/id/10414962

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
1999-8-16
pubmed:abstractText
Neuropeptide receptors couple via G-proteins to two principal signaling pathways that elevate cAMP through adenylate cyclase (AC) or mobilize intracellular Ca(2+) through phospholipase C (PLC)-stimulated inositol phosphate (IP) turnover and production of inositol 1,4,5-trisphosphate (IP(3)). We showed previously that high-affinity receptors for pituitary adenylate cyclase-activating polypeptide (PACAP) are present on chick ciliary ganglion neurons and that receptor occupation increases cAMP production, resulting in enhanced acetylcholine sensitivity. After we suppressed AC activity and cAMP production with 2'-5' dideoxyadenosine, however, PACAP no longer increased acetylcholine sensitivity but instead reduced it, suggesting that an AC-independent signal pathway activated by PACAP inhibits some nicotinic acetylcholine receptors (AChRs). We now use fast-perfusion, imaging, and biochemical methods to identify the AChRs modulated by PACAP and to characterize the signal pathway responsible for their inhibition. Without previous AC block, both the rapidly desensitizing, alpha-bungarotoxin (alphaBgt)-sensitive alpha7-AChRs and the slowly desensitizing, alphaBgt-insensitive alpha3*-AChRs on the neurons were potentiated by PACAP. After AC blockade, however, PACAP inhibited alpha7-AChRs but left alpha3*-AChRs unaffected. The selective inhibition of alpha7-AChRs appeared to use a PLC signaling pathway because it was not seen after lowering PLC activity or buffering intracellular Ca(2+) and was mimicked by dialyzing neurons with an IP(3) receptor agonist. PACAP also induced IP turnover and increased [Ca(2+)](i) assessed directly with Fluo-3AM imaging. Given our previous findings that PACAP receptors couple to AC, the present results demonstrate a remarkable ability of a single neuropeptide to activate two signaling pathways and in so doing selectively regulate two classes of downstream ion channel targets.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0270-6474
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6327-37
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Pituitary adenylate cyclase-activating polypeptide activates a phospholipase C-dependent signal pathway in chick ciliary ganglion neurons that selectively inhibits alpha7-containing nicotinic receptors.
pubmed:affiliation
Department of Anatomy and Neurobiology, Medical College of Ohio, Toledo, Ohio 43614-5804, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.