ArticleBehavioural brain research2009
Knockout of spinophilin, an endogenous antagonist of arrestin-dependent alpha2-adrenoceptor functions, enhances receptor-mediated antinociception yet does not eliminate sex-related differences.
Article in Behavioural brain research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed, 3 citations in OpenAlex.
- Spinophilin as a novel regulator of M3 muscarinic receptor-mediated insulin release in vitro and in vivo.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2012Article
- Enhanced hypotensive, bradycardic, and hypnotic responses to alpha2-adrenergic agonists in spinophilin-null mice are accompanied by increased G protein coupling to the alpha2A-adrenergic receptor.Molecular pharmacology · 2010Article
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Authors and funding
4 authors at 2 institutions in 1 country.
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Abstract
We have previously shown gonadal steroid-dependent, gender specific modulation of nociception by alpha(2)-adrenoceptors. Agonist activation of the receptor enhances its association with spinophilin that antagonizes arrestin functions both by diminishing receptor phosphorylation by G-protein-coupled receptor kinase 2 (GRK2) and by competing for receptor interactions with arrestin. Since spinophilin is highly enriched in dendritic spines, we investigated whether alpha(2)-adrenoceptor-induced antinociception as well as sex-related differences are modified in spinophilin knockout mice. We evaluated alpha(2)-adrenoceptor antinociception in a heat-evoked tail flick test in spinophilin wild type (Sp(+/+)) and knockout (Sp(-/-)) mice. Baseline tail flick latencies (TFLs) did not change between any groups. Interestingly, the alpha(2)-adrenoceptor agonist, clonidine, increased TFL in male and diestrous (low estrogen) Sp(-/-) as well as Sp(+/+) mice; in fact, this increase in TFL was significantly higher in Sp(-/-) male and diestrous groups than in their Sp(+/+) counterparts. This unexpected finding is consistent with enhanced alpha(2)-adrenoceptor-mediated sedation observed previously in Sp(-/-) mice, presumably due to accelerated endocytosis of desensitized receptors and recycling of refreshed receptors when arrestin is not competed for by spinophilin in Sp(-/-) mice. Despite modulation of alpha(2)-adrenoceptor effects in Sp(-/-) mice, sex-related differences were retained; thus, clonidine was ineffective in proestrous females (highest estrogen levels), in both Sp(-/-) and Sp(+/+) mice, reaffirming that estrogen suppresses alpha(2)-adrenoceptor-evoked antinociception. These findings show that elimination of spinophilin enhances alpha(2)-adrenoceptor-evoked antinociception in estrogen-deprived physiological settings, suggesting a role for spinophilin to suppress these effects, and yet this enhanced response cannot overcome the absence of antinociception with elevated estrogen levels.
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