Cellular distribution of the endothelin system in the human brain

• Published in: Journal of chemical neuroanatomy 2004-05, Vol.27 (2), p.87-98
• Main Authors: Naidoo, V, Naidoo, S, Mahabeer, R, Raidoo, D.M
• Format: Article
• Language: English
• Subjects: Adult; Aspartic Acid Endopeptidases - metabolism; Brain - anatomy & histology; Brain - metabolism; Brain Chemistry - physiology; Central nervous system; Endothelial Cells - metabolism; Endothelin-1 - metabolism; Endothelin-Converting Enzymes; Epithelial Cells - metabolism; Female; Humans; Immunohistochemistry; Immunoreactivity; Male; Medicin och hälsovetenskap; Metalloendopeptidases; Neurons - cytology; Neurons - metabolism; Neuropeptide; Receptors, Endothelin - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Vasoconstrictor
• ISSN: 0891-0618; 1873-6300
• DOI: 10.1016/j.jchemneu.2003.12.002

The vasoconstrictor endothelin-1 (ET-1) may also act as a neuropeptide. ET-1 is formed by the catalytic action of endothelin-converting enzyme-1 (ECE-1) on big ET-1 and its cellular actions are mediated via ET A and ET B receptors. Although localisation of these components in rodent brain has been extensively investigated, no single study has mapped their distribution in human brain. Here we describe the localisation of ET-1 mRNA, ET-1, ECE-1, ET A and ET B receptors within 24 human brain regions. In situ RT-PCR has previously detected ET-1 mRNA in 22 areas (excluding the post-central gyrus and pineal gland), and ET-1 immunoreactivity was visualised in cells of all regions. Using specific antibodies we have immunolocalised ECE-1 and ET B receptors in cells of 24 areas, and ET A receptors in nine regions (choroidal epithelial cells, neurones in the diencephalon, hippocampus, amygdaloid, dentate nucleus, Purkinje cells of the cerebellum, flocculo-nodular lobe and vermis). ET-1 mRNA, ET-1, ECE-1 and ET B receptors were observed in cortical pyramidal cells, neurones (brainstem, basal nuclei, thalamus, insula and claustrum, limbic region), cells in the anterior pituitary gland; nerve cell processes in the pars nervosa; pinealocytes and choroidal epithelial cells. Only ET-1 mRNA, ET-1, ECE-1, and ET B receptors were visualised in cerebral capillary endothelial cells. The presence of ET-1 mRNA, ECE-1 and ET-1 in 22 brain regions confirms ET expression and processing in human brain. The localisation of ET-1 and ET B receptors suggests receptor-mediated action akin to a neurotransmitter role for ET-1.