Linked Life Data

1331764

Source:http://linkedlifedata.com/resource/pubmed/id/1331764

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1992-12-9
pubmed:abstractText
Bovine pulmonary artery smooth muscle (SM) cells express a novel 5-hydroxytryptamine (5-HT) (5-HT4-like) receptor coupled to cAMP accumulation. cAMP radioimmunoassay established the agonist and antagonist profiles of this receptor. 5-HT (EC50 = 91 +/- 33 nM) and 5-methoxytryptamine were equipotent at the SM cell 5-HT receptor and both were more potent than 5-carboxamidotryptamine. Other tryptamine derivatives were less potent but remained full agonists. These findings are consistent with previous reports regarding 5-HT4 and 5-HT4-like receptors in the central nervous system. The most potent antagonists were the antidepressant compounds nortriptyline (IC50 = 177 +/- 153 nM) and zimelidine (IC50 = 202 +/- 101 nM). The 5-HT3 and 5-HT4 antagonist 3-tropanyl-indole-3-carboxylate (ICS 205-930) was also a competitive antagonist at this 5-HT4-like receptor (pA2 = 6.3). Antagonist affinities differed slightly at the SM cell receptor, compared with other 5-HT4 and 5-HT4-like receptors in the central nervous system. Nonetheless, the SM cell 5-HT4-like receptor displayed the same differential antagonist potencies as reported for these other receptors (ICS 205-930 > MDL 72222 and mianserin > ketanserin). 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was the most potent agonist for this 5-HT4-like receptor (EC50 = 6.4 +/- 3.4 nM). 8-OH-DPAT-induced cAMP accumulation could be blocked by ICS 205-930 but not by the 5-HT1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-pthalimido)butyl]piperazine hydrobromide, distinguishing the SM cell 5-HT receptor from 5-HT1A receptors. The mechanism of 5-HT-stimulated cAMP production was also investigated. First, GTP augmented basal and 5-HT-stimulated cAMP accumulation. Second, antisera to the carboxyl terminus of the alpha subunit of Gs, attenuated 5-HT-mediated adenylate cyclase activation. This established that 5-HT-stimulated cAMP accumulation in SM cells required GS. These findings suggest that SM cells express a novel 5-HT4-like receptor positively coupled to adenylate cyclase. An unexpected finding was that 8-OH-DPAT is a potent partial agonist. These studies suggest that there may be heterogeneity among 5-HT4-like receptors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
817-25
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
8-hydroxy-2-(di-n-propylamino)tetralin-responsive 5-hydroxytryptamine4-like receptor expressed in bovine pulmonary artery smooth muscle cells.
pubmed:affiliation
Medical Service (Nephrology), Department of Veterans Affairs Medical Center, Durham, North Carolina 27705.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't