High-affinity receptors for pituitary adenylate cyclase-activating polypeptide on chick ciliary ganglion neurons: Detection, intracellular signaling and relevance to nicotinic acetylcholine receptor function.
Item
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Title
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High-affinity receptors for pituitary adenylate cyclase-activating polypeptide on chick ciliary ganglion neurons: Detection, intracellular signaling and relevance to nicotinic acetylcholine receptor function.
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Identifier
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AAI9917683
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identifier
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9917683
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Creator
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Pardi, Desiree Ann.
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Contributor
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Adviser: Joseph F. Margiotta
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Date
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1999
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Neuroscience | Health Sciences, Pharmacology | Biology, Cell | Biology, Molecular
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Abstract
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Neuropeptide receptors that can couple to two major intracellular signaling pathways have been identified. One such receptor is an isoform of the pituitary adenylate cyclase-activating polypeptide (PACAP) receptor which elevates intracellular cAMP via stimulation of adenylate cyclase (AC), and induces release of intracellular calcium via phospholipase-C (PLC) stimulated inositol phosphate (IP) turnover. Previously, we showed that high-affinity (type I) PACAP receptors are present on chick ciliary ganglion neurons, and can stimulate the AC signaling pathway (Margiotta and Pardi, 1995) such that the resulting increase in cAMP enhances neuronal acetylcholine sensitivity (Margiotta, 1987). Using fast perfusion to identify nicotinic acetylcholine receptor (AChR) classes activated by nicotine, I now report that following AC blockade, PACAP receptor activation decreases the current produced by nicotine-induced activation of nicotinic receptors containing alpha7 subunits (A7-AChRs) leaving those receptors containing alpha3, alpha5, beta4 and beta2 subunits (alpha3*-AChRs) unaffected. The selective effect of PACAP on alpha7-AChRs utilized the PLC signaling pathway since it was blocked by buffering intracellular calcium with BAPTA, or by lowering PLC activity with U73122 and was mimicked by Inositol-1,4,5-triphosphate (IP3). PACAP also induced IP turnover in the neurons and increased intracellular calcium, assessed directly with Fluo-3AM imaging. These further indicate that the activated type I PACAP receptor can couple to PLC. Given our previous findings that PACAP receptors can couple to AC, increasing cAMP, the present results demonstrate a remarkable ability of a single neuropeptide to activate multiple neuronal signaling pathways, and in so doing, to selectively regulate specific classes of downstream ion channel targets depending on which pathway predominates.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
