Expression and function of alpha-adrenoceptors in zebrafish: drug effects, mRNA and receptor distributions

• Published in: Journal of neurochemistry 2005-09, Vol.94 (6), p.1559-1569
• Main Authors: Ruuskanen, Jori O, Peitsaro, Nina, Kaslin, Jan V M, Panula, Pertti, Scheinin, Mika
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-Agonists - pharmacology; Adrenergic alpha-Antagonists - pharmacology; Animals; Binding, Competitive - physiology; Brain - anatomy & histology; Brain - metabolism; Catecholamines - metabolism; Female; Isoquinolines - metabolism; Male; Mammals - anatomy & histology; Mammals - metabolism; Motor Activity - drug effects; Motor Activity - physiology; Naphthyridines - metabolism; Pigmentation - drug effects; Pigmentation - physiology; Radioligand Assay; Receptors, Adrenergic, alpha-2 - drug effects; Receptors, Adrenergic, alpha-2 - genetics; Receptors, Adrenergic, alpha-2 - metabolism; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Viscera - metabolism; Zebrafish - anatomy & histology; Zebrafish - metabolism
• ISSN: 0022-3042
• DOI: 10.1111/j.1471-4159.2005.03305.x

The alpha2-adrenoceptors are G-protein-coupled receptors that mediate many of the physiological effects of norepinephrine and epinephrine. Mammals have three subtypes of alpha2-adrenoceptors, alpha2A, alpha2B and alpha2C. Zebrafish, a teleost fish used widely as a model organism, has five distinct alpha2-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 alpha2-adrenoceptors, while two genes code for alpha2Da- and alpha2Db- adrenoceptors, representing a duplicated, fourth alpha2-adrenoceptor subtype. The three different mammalian alpha2-adrenoceptor subtypes have distinct expression patterns in different organs and tissues, and mediate different physiological functions. The zebrafish alpha2-adrenergic system, with five different alpha2-adrenoceptors, appears more complicated. In order to deduce the physiological functions of the zebrafish alpha2-adrenoceptors, we localized the expression of the five different alpha2-adrenoceptor subtypes using RT-PCR, mRNA in situ hybridization, and receptor autoradiography using the radiolabelled alpha2-adrenoceptor antagonist [ethyl-3H]RS-79948-197. Localization of the alpha2A-, alpha2B- and alpha2C-adrenoceptors in zebrafish shows marked conservation when compared with mammals. The zebrafish alpha2A, alpha2Da, and alpha2Db each partially follow the distribution pattern of the mammalian alpha2A: a possible indication of subfunction partitioning between these subtypes. The alpha2-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 alpha2-adrenoceptor agonist, dexmedetomidine. Both effects were antagonized by the specific alpha2-adrenoceptor antagonist atipamezole.