Effector coupling mechanisms of the cloned 5-HT1A receptor.

Details

Serval ID
serval:BIB_8537C32B9530
Type
Article: article from journal or magazin.
Collection
Publications
Title
Effector coupling mechanisms of the cloned 5-HT1A receptor.
Journal
Journal of Biological Chemistry
Author(s)
Fargin A., Raymond J.R., Regan J.W., Cotecchia S., Lefkowitz R.J., Caron M.G.
ISSN
0021-9258 (Print)
ISSN-L
0021-9258
Publication state
Published
Issued date
1989
Peer-reviewed
Oui
Volume
264
Number
25
Pages
14848-14852
Language
english
Abstract
The signal transduction pathways of the cloned human 5-HT1A receptor have been examined in two mammalian cell lines transiently (COS-7) or permanently (HeLa) expressing this receptor gene. In both systems, 5-hydroxytryptamine (5-HT, serotonin) mediated a marked inhibition of beta 2-adrenergic agonist-stimulated (80% inhibition in COS-7 cells) or forskolin-stimulated cAMP formation (up to 90% inhibition in HeLa cells). This serotonin effect (EC50 = 20 nM) could be competitively antagonized by metitepine and spiperone (Ki = 81 and 31 nM, respectively) and could also be blocked by pretreatment of cells with pertussis toxin. In both cell types, 5-HT failed to stimulate adenylyl cyclase through the expressed receptors. In HeLa cells, 5-HT also stimulated phospholipase C (approximately 40-75% stimulation of formation of inositol phosphates). Again, this effect was inhibited by metitepine. However, the EC50 of 5-HT was considerably higher (approximately 3.2 microM) than that found for inhibition of adenylyl cyclase. Both pathways were demonstrated to be similarly affected by pertussis toxin. These findings indicate that like the M2 and M3 muscarinic cholinergic receptors, the 5-HT1A receptor can couple to multiple transduction pathways with varying efficiencies via pertussis toxin-sensitive G-proteins. The lack of stimulation of cAMP formation by this 5-HT1A receptor may suggest the existence of another pharmacologically closely related receptor.
Keywords
Adenylate Cyclase Toxin, Animals, Cell Line, Cercopithecus aethiops, Cloning, Molecular, Cyclic AMP/metabolism, Forskolin/pharmacology, HeLa Cells, Humans, Hydrolysis, Kidney, Pertussis Toxin, Phosphatidylinositols/metabolism, Phosphatidylinositols/physiology, Receptors, Serotonin/drug effects, Receptors, Serotonin/genetics, Signal Transduction/drug effects, Transfection, Virulence Factors, Bordetella/pharmacology
Pubmed
Web of science
Create date
24/01/2008 12:05
Last modification date
20/08/2019 15:44
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