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Multiple second messenger pathways of alpha-adrenergic receptor subtypes expressed in eukaryotic cells.

Publication ,  Journal Article
Cotecchia, S; Kobilka, BK; Daniel, KW; Nolan, RD; Lapetina, EY; Caron, MG; Lefkowitz, RJ; Regan, JW
Published in: J Biol Chem
January 5, 1990

The alpha-adrenergic receptors mediate the effects of epinephrine and norepinephrine on cellular signaling systems via guanine nucleotide binding regulatory proteins (G-proteins). Three alpha-adrenergic receptor subtypes have been cloned: the alpha 1, the alpha 2-C10, and the alpha 2-C4 adrenergic receptors. To investigate functional differences between the different subtypes, we assessed the ability of each to interact with adenylyl cyclase and polyphosphoinositide metabolism by permanently and transiently expressing the DNAs encoding the alpha 1, the alpha 2-C10, and the alpha 2-C4 adrenergic receptors in cells lacking endogenous alpha-adrenergic receptors. Both alpha 2-C10 and alpha 2-C4 couple primarily to inhibition of adenylyl cyclase and to a lesser extent to stimulation of polyphosphoinositide hydrolysis. alpha 2-C10 inhibits adenylyl cyclase more efficiently than alpha 2-C4. Effects of the alpha 2-adrenergic receptors on adenylyl cyclase inhibition and on polyphosphoinositide hydrolysis are both mediated by pertussis toxin-sensitive G-proteins. The major coupling system of the alpha 1-adrenergic receptor is activation of phospholipase C via a pertussis toxin-insensitive G-protein. alpha 1-Adrenergic receptor stimulation can also increase intracellular cAMP by a mechanism that does not involve direct activation of adenylyl cyclase. As with the muscarinic cholinergic receptor family our results show that each of the alpha-adrenergic receptor subtypes can couple to multiple signal transduction pathways and suggest several generalities about the effector coupling mechanisms of G-protein-coupled receptors.

Duke Scholars

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

January 5, 1990

Volume

265

Issue

1

Start / End Page

63 / 69

Location

United States

Related Subject Headings

  • Virulence Factors, Bordetella
  • Type C Phospholipases
  • Transfection
  • Signal Transduction
  • Second Messenger Systems
  • Receptors, Adrenergic, alpha
  • Phosphatidylinositols
  • Pertussis Toxin
  • Hydrolysis
  • Gene Expression
 

Citation

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Cotecchia, S., Kobilka, B. K., Daniel, K. W., Nolan, R. D., Lapetina, E. Y., Caron, M. G., … Regan, J. W. (1990). Multiple second messenger pathways of alpha-adrenergic receptor subtypes expressed in eukaryotic cells. J Biol Chem, 265(1), 63–69.
Cotecchia, S., B. K. Kobilka, K. W. Daniel, R. D. Nolan, E. Y. Lapetina, M. G. Caron, R. J. Lefkowitz, and J. W. Regan. “Multiple second messenger pathways of alpha-adrenergic receptor subtypes expressed in eukaryotic cells.J Biol Chem 265, no. 1 (January 5, 1990): 63–69.
Cotecchia S, Kobilka BK, Daniel KW, Nolan RD, Lapetina EY, Caron MG, et al. Multiple second messenger pathways of alpha-adrenergic receptor subtypes expressed in eukaryotic cells. J Biol Chem. 1990 Jan 5;265(1):63–9.
Cotecchia, S., et al. “Multiple second messenger pathways of alpha-adrenergic receptor subtypes expressed in eukaryotic cells.J Biol Chem, vol. 265, no. 1, Jan. 1990, pp. 63–69.
Cotecchia S, Kobilka BK, Daniel KW, Nolan RD, Lapetina EY, Caron MG, Lefkowitz RJ, Regan JW. Multiple second messenger pathways of alpha-adrenergic receptor subtypes expressed in eukaryotic cells. J Biol Chem. 1990 Jan 5;265(1):63–69.

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

January 5, 1990

Volume

265

Issue

1

Start / End Page

63 / 69

Location

United States

Related Subject Headings

  • Virulence Factors, Bordetella
  • Type C Phospholipases
  • Transfection
  • Signal Transduction
  • Second Messenger Systems
  • Receptors, Adrenergic, alpha
  • Phosphatidylinositols
  • Pertussis Toxin
  • Hydrolysis
  • Gene Expression