Differential expression of two alpha 2-adrenergic receptor subtype mRNAs in human tissues.
Genetic subtypes of alpha 2-adrenergic receptors (AR) may mediate distinct physiological functions, and undergo differential cell type-specific regulation. Thus, these distinct receptor subtypes are possible targets for the development of subtype-selective drugs. We have analyzed the tissue distribution of two human alpha 2-adrenoceptor subtype gene mRNAs, alpha 2-C4 and alpha 2-C10, in normal human fetal and adult tissues. Both receptor subtype mRNAs were abundantly expressed in fetal brain and choroid plexus. In non-neural fetal tissues, alpha 2-C10 mRNA was detected in spleen, kidney, adrenal gland, and skin, while alpha 2-C4 transcripts were observed only in kidney and skin. Most regions of the adult brain also expressed both subtypes, but with marked quantitative differences. For example, cerebral cortex contained predominantly alpha 2-C10 mRNA, whereas the caudate nucleus expressed mostly alpha 2-C4 mRNA. In adult peripheral tissues, alpha 2-C10 mRNA expression was most abundant in spleen and renal cortex, and expression of alpha 2-C4 mRNA was strongest in renal cortex and medulla. These different expression patterns provide evidence for the differential regulation of the two alpha 2-adrenergic receptor genes and warrant further investigation with techniques capable of improved anatomical resolution. Regional differences in receptor subtype expression may be valuable for the development of new, subtype-selective pharmacological agents with more targeted actions compared to currently used alpha 2-adrenoceptor agonists and antagonists.
Perälä
M
M
Department of Biochemistry, Abo Akademi, Turku, Finland.
Hirvonen
H
H
Kalimo
H
H
Ala-Uotila
S
S
Regan
J W
JW
Akerman
K E
KE
Scheinin
M
M
D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D009693:Nucleic Acid Hybridization; D009928:Organ Specificity / Q000502:physiology; D015347:RNA Probes; D016372:RNA, Antisense / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis*; D011942:Receptors, Adrenergic, alpha / Q000235:genetics*; D012260:Ribonucleases; D014781:Viscera / Q000196:embryology / Q000378:metabolism*
D015347:RNA Probes; D016372:RNA, Antisense; D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; D012260:Ribonucleases