Alpha1-adrenoreceptor in human hippocampus: binding and receptor subtype mRNA expression.
Alpha1-adrenoreceptors (AR), of which three subtypes exist (alpha1A-, alpha1B- and alpha1D-AR) are G-protein-coupled receptors that mediate the actions of norepinephrine and epinephrine both peripherally and centrally. In the CNS, alpha1-ARs are found in the hippocampus where animal studies have shown the ability of alpha1-AR agents to modulate long-term potentiation and memory; however, the precise distribution of alpha1-AR expression and its subtypes in the human brain is unknown making functional comparisons difficult. In the human hippocampus, 3H-prazosin (alpha1-AR antagonist) labels only the dentate gyrus (molecular, granule and polymorphic layers) and the stratum lucidum of the CA3 homogeneously. Human alpha1A-AR mRNA in the hippocampus is observed only in the dentate gyrus granule cell layer, while alpha1D-AR mRNA expression is observed only in the pyramidal cell layers of CA1, CA2 and CA3, regions where 3H-prazosin did not bind. alpha1B-AR mRNA is not expressed at detectable levels in the human hippocampus. These results confirm a difference in hippocampal alpha1-AR localization between rat and humans and further describe a difference in the localization of the alpha1A- and alpha1D-AR mRNA subtype between rats and humans.
Szot
Patricia
P
Northwest Network Mental Illness Research, Education and Clinical Center (S-116), VA Puget Sound Health Care System, S-116 MIRECC, 1660 S. Columbian Way, Seattle, WA 98108, USA. szot@u.washington.edu
White
Sylvia S
SS
Greenup
J Lynne
JL
Leverenz
James B
JB
Peskind
Elaine R
ER
Raskind
Murray A
MA
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011180:Postmortem Changes; D011485:Protein Binding / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011869:Radioligand Assay / Q000379:methods; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014316:Tritium / Q000493:pharmacokinetics
D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D014316:Tritium