Expression and function of α2-adrenoceptors in zebrafish: Drug effects, mRNA and receptor distributions

The α₂-adrenoceptors are G-protein-coupled receptors that mediate many of the physiological effects of norepinephrine and epinephrine. Mammals have three subtypes of α₂-adrenoceptors, α_2A, α_2B and α_2C. Zebrafish, a teleost fish used widely as a model organism, has five distinct α₂-adrenoceptor genes. The zebrafish has emerged as a powerful tool to study development and genetics, with many mutations causing diseases reminiscent of human diseases. Three of the zebrafish adra2 genes code for orthologues of the mammalian α₂-adrenoceptors, while two genes code for α_2Da- and α_2Db- adrenoceptors, representing a duplicated, fourth α₂-adrenoceptor subtype. The three different mammalian α₂-adrenoceptor subtypes have distinct expression patterns in different organs and tissues, and mediate different physiological functions. The zebrafish α₂-adrenergic system, with five different α₂-adrenoceptors, appears more complicated. In order to deduce the physiological functions of the zebrafish α₂-adrenoceptors, we localized the expression of the five different α₂-adrenoceptor subtypes using RT-PCR, mRNA in situ hybridization, and receptor autoradiography using the radiolabelled α₂-adrenoceptor antagonist [ethyl-³H]RS-79948-197. Localization of the α_2A-, α_2B- and α_2C-adrenoceptors in zebrafish shows marked conservation when compared with mammals. The zebrafish α_2A, α _2Da, and α_2Db each partially follow the distribution pattern of the mammalian α_2A: a possible indication of subfunction partitioning between these subtypes. The α₂- adrenergic system is functional in zebrafish also in vivo, as demonstrated by marked locomotor inhibition, similarly to mammals, and lightening of skin colour induced by the specific α₂-adrenoceptor agonist, dexmedetomidine. Both effects were antagonized by the specific α₂-adrenoceptor antagonist atipamezole.