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

S. Cotecchia, B. K. Kobilka, K. W. Daniel, R. D. Nolan, E. Y. Lapetina, M. G. Caron, R. J. Lefkowitz, J. W. Regan

Research output: Contribution to journalArticle

227 Scopus citations

Abstract

The α-adrenergic receptors mediate the effects of epinephrine and norepinephrine on cellular signaling systems via guanine nucleotide binding regulatory proteins (G-proteins). Three α-adrenergic receptor subtypes have been cloned: the α1, the α2-C10, and the α2-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 α1, the α2-C10, and the α2-C4 adrenergic receptors in cells lacking endogenous α-adrenergic receptors. Both α2-C10 and α2-C4 couple primarily to inhibition of adenylyl cyclase and to a lesser extent to stimulation of polyphosphoinositide hydrolysis. α2-C10 inhibits adenylyl cyclase more efficiently than α2-C4. Effects of the α2-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 α1-adrenergic receptor is activation of phospholipase C via a pertussis toxin-insensitive G-protein. α1-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 α-adrenergic receptor subtypes can couple to multiple signal transduction pathways and suggest several generalities about the effector coupling mechanisms of G-protein-coupled receptors.

Original languageEnglish (US)
Pages (from-to)63-69
Number of pages7
JournalJournal of Biological Chemistry
Volume265
Issue number1
StatePublished - 1990

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Cotecchia, S., Kobilka, B. K., Daniel, K. W., Nolan, R. D., Lapetina, E. Y., Caron, M. G., Lefkowitz, R. J., & Regan, J. W. (1990). Multiple second messenger pathways of α-adrenergic receptor subtypes expressed in eukaryotic cells. Journal of Biological Chemistry, 265(1), 63-69.