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

J Neurochem. 2005 Sep;94(6):1559-69. doi: 10.1111/j.1471-4159.2005.03305.x. Epub 2005 Jul 5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism*
  • Radioligand Assay
  • Receptors, Adrenergic, alpha-2 / drug effects
  • Receptors, Adrenergic, alpha-2 / genetics
  • Receptors, Adrenergic, alpha-2 / metabolism*
  • Viscera / metabolism
  • Zebrafish / anatomy & histology
  • Zebrafish / metabolism*


  • ADRA2A protein, human
  • ADRA2B protein, human
  • ADRA2C protein, human
  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Catecholamines
  • Isoquinolines
  • Naphthyridines
  • RNA, Messenger
  • RS 79948-197
  • Receptors, Adrenergic, alpha-2