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Effector coupling mechanisms of the cloned 5-HT1A receptor.

Publication ,  Journal Article
Fargin, A; Raymond, JR; Regan, JW; Cotecchia, S; Lefkowitz, RJ; Caron, MG
Published in: J Biol Chem
September 5, 1989

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.

Duke Scholars

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

September 5, 1989

Volume

264

Issue

25

Start / End Page

14848 / 14852

Location

United States

Related Subject Headings

  • Virulence Factors, Bordetella
  • Transfection
  • Signal Transduction
  • Receptors, Serotonin
  • Phosphatidylinositols
  • Pertussis Toxin
  • Kidney
  • Hydrolysis
  • Humans
  • Hela Cells
 

Citation

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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. J Biol Chem, 264(25), 14848–14852.
Fargin, A., J. R. Raymond, J. W. Regan, S. Cotecchia, R. J. Lefkowitz, and M. G. Caron. “Effector coupling mechanisms of the cloned 5-HT1A receptor.J Biol Chem 264, no. 25 (September 5, 1989): 14848–52.
Fargin A, Raymond JR, Regan JW, Cotecchia S, Lefkowitz RJ, Caron MG. Effector coupling mechanisms of the cloned 5-HT1A receptor. J Biol Chem. 1989 Sep 5;264(25):14848–52.
Fargin, A., et al. “Effector coupling mechanisms of the cloned 5-HT1A receptor.J Biol Chem, vol. 264, no. 25, Sept. 1989, pp. 14848–52.
Fargin A, Raymond JR, Regan JW, Cotecchia S, Lefkowitz RJ, Caron MG. Effector coupling mechanisms of the cloned 5-HT1A receptor. J Biol Chem. 1989 Sep 5;264(25):14848–14852.

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

September 5, 1989

Volume

264

Issue

25

Start / End Page

14848 / 14852

Location

United States

Related Subject Headings

  • Virulence Factors, Bordetella
  • Transfection
  • Signal Transduction
  • Receptors, Serotonin
  • Phosphatidylinositols
  • Pertussis Toxin
  • Kidney
  • Hydrolysis
  • Humans
  • Hela Cells