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  • Title: Inhibitors of serine/threonine protein phosphatases antagonize the antinociception induced by agonists of alpha 2 adrenoceptors and GABAB but not kappa-opioid receptors in the tail flick test in mice.
    Author: Moncada A, Cendán CM, Baeyens JM, Del Pozo E.
    Journal: Pain; 2005 Mar; 114(1-2):212-20. PubMed ID: 15733647.
    Abstract:
    We previously reported that serine/threonine protein phosphatases (PPs) play a role in the antinociception induced by the mu-opioid receptor agonist morphine. In this study we evaluated the possible involvement of PPs on the antinociception induced by agonists of others G protein-coupled receptors in the tail flick test in mice. The subcutaneous administration of clonidine (0.25-4 mg/kg), baclofen (2-32 mg/kg) or U50,488H (2-16 mg/kg) (agonists of alpha(2) adrenoceptors, GABA(B) and kappa-opioid receptors, respectively) produced dose-dependent antinociception. The antinociceptive effects of clonidine and baclofen were antagonized in a dose-dependent way by the protein phosphatase inhibitors okadaic acid (0.001-10 pg/mouse, i.c.v.) and cantharidin (0.001-10 ng/mouse, i.c.v.), and okadaic acid was 1000 times more potent than cantharidin in producing this effect. The effects of these drugs appear to be specifically due to the blockade of PPs, since L-norokadaone (an analogue of okadaic acid that has no effect on PPs) did not modify clonidine- or baclofen-induced antinociception over the wide range of doses used (0.001-1000 pg/mouse, i.c.v.). On the other hand, the antinociception induced by activation of kappa-opioid receptors with U50,488H was not modified by okadaic acid or cantharidin. In conclusion, our data support the idea that serine/threonine PPs are differentially involved in the antinociceptive effects of several agonists of G protein-coupled receptors in mice.
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