Effector coupling mechanisms of the cloned 5-HT1A receptor

A. Fargin, J. R. Raymond, John W Regan, S. Cotecchia, R. J. Lefkowitz, M. G. Caron

Research output: Contribution to journalArticle

245 Citations (Scopus)

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 β2-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 (K(i) = 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 (~40-75% stimulation of formation of inositol phosphates). Again this effect was inhibited by metitepine. However, the EC50 of 5-HT was considerably higher (~3.2 μM) than that found for inhibition of adenylyl cyclase. Both pathways were demonstrated to be similarly effected 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.

Original languageEnglish (US)
Pages (from-to)14848-14852
Number of pages5
JournalJournal of Biological Chemistry
Volume264
Issue number25
StatePublished - 1989
Externally publishedYes

Fingerprint

Receptor, Serotonin, 5-HT1A
Serotonin
Pertussis Toxin
Methiothepin
HeLa Cells
Adenylyl Cyclases
Cells
Serotonin Agents
Spiperone
Signal transduction
Adrenergic Agonists
Inositol Phosphates
COS Cells
Type C Phospholipases
Cholinergic Receptors
Muscarinic Receptors
Colforsin
GTP-Binding Proteins
Cholinergic Agents
Signal Transduction

ASJC Scopus subject areas

  • Biochemistry

Cite this

Fargin, A., Raymond, J. R., Regan, J. W., Cotecchia, S., Lefkowitz, R. J., & Caron, M. G. (1989). Effector coupling mechanisms of the cloned 5-HT1A receptor. Journal of Biological Chemistry, 264(25), 14848-14852.

Effector coupling mechanisms of the cloned 5-HT1A receptor. / Fargin, A.; Raymond, J. R.; Regan, John W; Cotecchia, S.; Lefkowitz, R. J.; Caron, M. G.

In: Journal of Biological Chemistry, Vol. 264, No. 25, 1989, p. 14848-14852.

Research output: Contribution to journalArticle

Fargin, A, Raymond, JR, Regan, JW, Cotecchia, S, Lefkowitz, RJ & Caron, MG 1989, 'Effector coupling mechanisms of the cloned 5-HT1A receptor', Journal of Biological Chemistry, vol. 264, no. 25, pp. 14848-14852.
Fargin A, Raymond JR, Regan JW, Cotecchia S, Lefkowitz RJ, Caron MG. Effector coupling mechanisms of the cloned 5-HT1A receptor. Journal of Biological Chemistry. 1989;264(25):14848-14852.
Fargin, A. ; Raymond, J. R. ; Regan, John W ; Cotecchia, S. ; Lefkowitz, R. J. ; Caron, M. G. / Effector coupling mechanisms of the cloned 5-HT1A receptor. In: Journal of Biological Chemistry. 1989 ; Vol. 264, No. 25. pp. 14848-14852.
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