title: Distribution of 5-ht(1E)  receptors in the mammalian brain and cerebral vasculature: an immunohistochemical and pharmacological study.
abstract: OBJECTIVE
  The 5-ht(1E) receptor is highly expressed in the human brain and its structure is conserved in humans, suggesting an important physiological role for 5-ht(1E) receptors. However, neither the function nor the distribution of this receptor has been characterized in the mammalian brain.
  
  
  METHODS
  Rats and mice lack the 5-ht(1E) receptor gene; thus, we used guinea pig brain tissue and immunofluorescent staining techniques to provide the first specific localization of 5-ht(1E) receptors in the mammalian brain.
  
  
  RESULTS
  High levels of 5-ht(1E) receptors are detected in olfactory bulb glomeruli as well as the molecular layer of the dentate gyrus (DG). In DG membranes, BRL54443, a 5-ht(1E) /5-HT(1F) agonist, selectively stimulated 5-ht(1E) receptors and potently inhibited forskolin-dependent cAMP production (IC₅₀ = 14 nM). The staining pattern of 5-ht(1E) receptors in brain tissue suggests that this receptor is expressed predominantly in neurons rather than in glia. Additionally, 5-ht(1E) receptors were detected in the adventitial layer of cerebral arteries but not in the microvasculature, venous tissue or other brain arteries.
  
  
  CONCLUSIONS
  These observations should help to predict clinical effects of 5-ht(1E) -selective drugs. For example, the stimulation of 5-ht(1E) receptors and subsequent inhibition of adenylate cyclase activity in the DG suggests that 5-ht(1E) receptors may mediate regulation of hippocampal activity by 5-HT, making it a possible drug target for the treatment of neuropsychiatric disorders characterized by memory deficits (such as Alzheimer's disease) or as a target for the treatment of temporal lobe epilepsy.
authors.affiliation: Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY 12208, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Klein
authors.forename: M
authors.initials: M
authors.lastname: Teitler
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D001921:Brain / Q000098:blood supply / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002536:Cerebral Arteries / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003238:Connective Tissue / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D058990:Molecular Targeted Therapy; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology; D013045:Species Specificity
chemical_list: D009419:Nerve Tissue Proteins; D011985:Receptors, Serotonin; D058825:Serotonin 5-HT1 Receptor Agonists; C076396:serotonin 1E receptor; D000242:Cyclic AMP