Elsevier

Neuroscience Letters

Volume 299, Issues 1–2, 16 February 2001, Pages 25-28
Neuroscience Letters

Opioid-induced adenylyl cyclase supersensitization in human embryonic kidney 293 cells requires pertussis toxin-sensitive G proteins other than Gi1 and Gi3

https://doi.org/10.1016/S0304-3940(00)01772-9Get rights and content

Abstract

Chronic activation of opioid receptors in cultured mammalian cells is known to induce adenylyl cyclase (AC) supersensitization via the pertussis toxin-sensitive Gi/o proteins. To examine the role of Gi1 and Gi3 in opioid-induced AC supersensitization, pertussis toxin-resistant mutants of Gαi1 and Gαi3 (Gαi1CG and Gαi3CG) were stably co-expressed with different opioid receptors (μ, δ or κ) in human embryonic kidney (HEK 293) cells. Although the opioid receptors were capable of inhibiting AC via Gαi1CG and Gαi3CG in pertussis toxin-treated cells, AC supersensitization induced by chronic opioid treatment remained sensitive to pertussis toxin. Our results demonstrated that despite their ability to interact with opioid receptors, the pertussis toxin-sensitive Gi1 and Gi3 proteins on their own are incapable of supporting opioid-induced AC supersensitization.

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Acknowledgements

This work was supported in part by the Hong Kong Jockey Club and the Research Grants Council of Hong Kong (HKUST 567/95M and HKUST 6096/98M).

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  • Gα<inf>i/o</inf>-coupled receptor-mediated sensitization of adenylyl cyclase: 40 years later

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    Pretreatment with pertussis toxin leads to ADP-ribosylation of Gαi/o subunits, ultimately preventing their activation by receptors. Because pertussis toxin inhibits all isoforms of Gαi (i.e. Gαi1, Gαi2, Gαi3), and Gαo (Gαoa and Gαob), pertussis toxin insensitive (PTXi) isoforms of inhibitory Gα have been employed to determine the isoforms involved in heterologous sensitization for a number of receptors (Clark et al., 2004; Taussig et al., 1992; Tso and Wong, 2000, 2001; Watts et al., 1998; Zhang et al., 2006). Despite receptor dependency, PTXi-Gαo robustly rescued sensitization through the dopamine D2 receptor and μ-opioid receptor (Clark et al., 2004; Watts et al., 1998).

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