Expression and function of α2‐adrenoceptors in zebrafish: drug effects, mRNA and receptor distributions

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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, α2Da, 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.