Expression and function of alpha-adrenoceptors in zebrafish: drug effects, mRNA and receptor distributions.
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.
Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland.
Jori O
JO
Ruuskanen
Nina
N
Peitsaro
Jan V M
JV
Kaslin
Pertti
P
Panula
Mika
M
Scheinin
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D005260:Female; D007546:Isoquinolines / Q000378:metabolism; D008297:Male; D008322:Mammals / Q000033:anatomy & histology / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009287:Naphthyridines / Q000378:metabolism; D010858:Pigmentation / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D011869:Radioligand Assay; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014781:Viscera / Q000378:metabolism; D015027:Zebrafish / Q000033:anatomy & histology / Q000378:metabolism*
C547768:ADRA2A protein, human; C547771:ADRA2B protein, human; C547774:ADRA2C protein, human; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002395:Catecholamines; D007546:Isoquinolines; D009287:Naphthyridines; D012333:RNA, Messenger; C104875:RS 79948-197; D018341:Receptors, Adrenergic, alpha-2