Distribution of 5-ht(1E) receptors in the mammalian brain and cerebral vasculature: an immunohistochemical and pharmacological study.

BACKGROUND AND PURPOSE: 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.

EXPERIMENTAL APPROACH: 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.

KEY 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 AND IMPLICATIONS: 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.