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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1988-8-17
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pubmed:abstractText |
The nonselective alpha-adrenergic agonist oxymetazoline inhibits parathyroid hormone (PTH)-stimulated cAMP production in intact OK cells, an epithelial cell line derived from an American opossum kidney. This inhibition, however, is not blocked by alpha 2-adrenergic receptor antagonists. After excluding several alternate hypotheses to explain this anomalous activity of oxymetazoline, we hypothesized that oxymetazoline activates a receptor in OK cells that is negatively coupled to adenylate cyclase but distinct from the alpha 2-adrenergic receptor. Prior exposure of OK cells to pertussis toxin blocks the inhibitory response to oxymetazoline, suggesting involvement of a guanine nucleotide-binding regulatory protein. Screening various compounds for attenuation of PTH-stimulated adenylate cyclase showed that serotonin (5HT) is a potent and fully efficacious agonist. Desensitization of alpha 2-receptor-mediated inhibition of cAMP production by epinephrine did not alter the response to either 5HT or oxymetazoline, indicating that these compounds do not produce their effect by activating alpha 2-adrenergic receptors. The 5HT1 receptor-selective antagonist methiothepin, but not ketanserin (5HT2-selective) or ICS-205,930 (5HT3-selective), blocked the response to both 5HT and oxymetazoline. The potency of methiothepin for antagonizing oxymetazoline-induced inhibition of PTH-stimulated cAMP production was not significantly different from its potency for the 5HT-induced effect. These data indicate that OK cells express a 5HT1 receptor that is negatively coupled to adenylate cyclase and that oxymetazoline is an agonist at these receptors.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Methiothepin,
http://linkedlifedata.com/resource/pubmed/chemical/Oxymetazoline,
http://linkedlifedata.com/resource/pubmed/chemical/Parathyroid Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0026-895X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
34
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1-7
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:2839761-Adenylate Cyclase,
pubmed-meshheading:2839761-Binding Sites,
pubmed-meshheading:2839761-Cell Line,
pubmed-meshheading:2839761-Cyclic AMP,
pubmed-meshheading:2839761-Imidazoles,
pubmed-meshheading:2839761-Kidney,
pubmed-meshheading:2839761-Methiothepin,
pubmed-meshheading:2839761-Oxymetazoline,
pubmed-meshheading:2839761-Parathyroid Hormone,
pubmed-meshheading:2839761-Receptors, Adrenergic, alpha,
pubmed-meshheading:2839761-Receptors, Serotonin
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pubmed:year |
1988
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pubmed:articleTitle |
Oxymetazoline inhibits adenylate cyclase by activation of serotonin-1 receptors in the OK cell, an established renal epithelial cell line.
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pubmed:affiliation |
Department of Pharmacology, School of Medicine, University of Missouri-Columbia 65212.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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