Heterologous desensitization and reduced G protein ADP-ribosylation following exposure to α2-adrenoceptor and muscarinic receptor agonists

Seung Yeol Nah, Bernard Attali, Zvi Vogel

Research output: Contribution to journalArticlepeer-review

Abstract

We investigated the acute and chronic effects of α2-adrenoceptor and muscarinic receptor agonists on dihydropyridine-sensitive voltage-dependent Ca2+ channels in spinal cord-dorsal root ganglion cocultures. Clonidine and oxotremorine inhibited the voltage-dependent Ca2+ influx (42 ± 2% and 35 ± 6% with 100 μM, respectively). The respective antagonists, yohimbine and atropine, abolished these effects.Pertussis toxin attenuated the inhibitory effects of clonidine and oxotremorine on Ca2+ influx, demonstrating involvement of G proteins in the transduction process. Chronic treatment with clonidine or oxotremorine desensitized the Ca2+ channel response to the agonist applied as well as to other receptor agonist (heterologous desensitization). Such treatment with clonidine or oxotremorine decreased the pertussin toxin-catalyzed ADP-ribosylation of G and G subunits, an effect which could be largely reversed by the detergent Lubrol PX. Yohimbine and atropine blocked the effects of clonidine or oxotremorine on pertussis toxin-catalyzed ADP-ribosylation. Results suggest that α2-adrenoceptor and muscarinic receptors couple to the dihydropyridine-sensitive voltage-dependent Ca2+ channels via pertussis toxin-sensitive G proteins. Chronic agonist treatment leads to heterologous desensitization and to a reduced capacity of Gi and Go to undergo pertussis toxin-catalyzed ADP-ribosylation.

Original languageEnglish
Pages (from-to)67-75
Number of pages9
JournalEuropean Journal of Pharmacology: Molecular Pharmacology
Volume244
Issue number1
DOIs
StatePublished - 4 Jan 1993
Externally publishedYes

Keywords

  • ADP ribosylation
  • Ca channels
  • GTP-binding proteins
  • Heterologous desensitization
  • Muscarinic receptors
  • α-Adrenoceptors

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