%0 Journal Article %A Jukka Sallinen %A Richard E. Link %A Antti Haapalinna %A Timo Viitamaa %A Maya Kulatunga %A Birgitta Sjöholm %A Ewen Macdonald %A Markku Pelto-Huikko %A Tiina Leino %A Gregory S. Barsh %A Brian K. Kobilka %A Mika Scheinin %T Genetic Alteration of α2C-Adrenoceptor Expression in Mice: Influence on Locomotor, Hypothermic, and Neurochemical Effects of Dexmedetomidine, a Subtype-Nonselective α2-Adrenoceptor Agonist %D 1997 %R 10.1124/mol.51.1.36 %J Molecular Pharmacology %P 36-46 %V 51 %N 1 %X α2-Adrenergic receptors (α2-ARs) regulate many physiological functions and are targets for clinically important antihypertensive and anesthetic agents. Three human and mouse genes encoding α2-AR subtypes (α2A, α2B, and α2C) have been cloned. We investigated the involvement of the α2C-AR in α2-adrenergic pharmacology by applying molecular genetic techniques to alter the expression of α2C-AR in mice. The effects of dexmedetomidine, a subtype-nonselective α2-AR agonist, on monoamine turnover in brain and on locomotor activity were similar in mice with targeted inactivation of the α2C-AR gene and in their controls, but the hypothermic effect of the α2-AR agonist was significantly attenuated by the receptor gene inactivation. Correspondingly, another strain of transgenic mice with 3-fold overexpression of α2C-AR in striatum and other brain regions expressing α2C-AR showed normal reductions in brain monoamine metabolism and locomotor activity after dexmedetomidine, but their hypothermic response to the α2-AR agonist was significantly accentuated. The hypothermic effect of α2-AR agonists thus seems to be mediated in part by α2C-AR. Some small but statistically significant differences between the strains were also noted in brain dopamine metabolism. Lack of α2C-AR expression was linked with reduced levels of homovanillic acid in brain, and mice with increased α2C-AR expression had elevated concentrations of the dopamine metabolite compared with their controls. %U https://molpharm.aspetjournals.org/content/molpharm/51/1/36.full.pdf