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

Abstract

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, α2A, α2B and α2C. 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 α2Da- and α2Db- 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 α2A-, α2B- and α2C-adrenoceptors in zebrafish shows marked conservation when compared with mammals. The zebrafish α2A, α 2Da, and α2Db each partially follow the distribution pattern of the mammalian α2A: 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. © 2005 International Society for Neurochemistry.