Expression and function of α 2 ‐adrenoceptors in zebrafish: drug effects, mRNA and receptor distributions

The α 2 ‐adrenoceptors are G‐protein‐coupled receptors that mediate many of the physiological effects of norepinephrine and epinephrine. Mammals have three subtypes of α 2 ‐adrenoceptors, α 2A , α 2B and α 2C . Zebrafish, a teleost fish used widely as a model organism, has five distinct α 2 ‐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 α 2 ‐adrenoceptors, while two genes code for α 2Da ‐ and α 2Db ‐ adrenoceptors, representing a duplicated, fourth α 2 ‐adrenoceptor subtype. The three different mammalian α 2 ‐adrenoceptor subtypes have distinct expression patterns in different organs and tissues, and mediate different physiological functions. The zebrafish α 2 ‐adrenergic system, with five different α 2 ‐adrenoceptors, appears more complicated. In order to deduce the physiological functions of the zebrafish α 2 ‐adrenoceptors, we localized the expression of the five different α 2 ‐adrenoceptor subtypes using RT–PCR, mRNA in situ hybridization, and receptor autoradiography using the radiolabelled α 2 ‐adrenoceptor antagonist [ethyl‐ 3 H]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 α 2 ‐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 α 2 ‐adrenoceptor agonist, dexmedetomidine. Both effects were antagonized by the specific α 2 ‐adrenoceptor antagonist atipamezole.