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Endothelin in Human Brain and Pituitary Gland: Presence of Immunoreactive Endothelin, Endothelin Messenger Ribonucleic Acid, and Endothelin Receptors

Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital London W12 ONN
Department of Histopathology and Cytopathology (J.K.M.), York District Hospital York YO3 7HE, United Kingdom

Address all correspondence and requests for reprints to: Professor S. R. Bloom, Department of Medicine, Francis Fraser Laboratory, 2nd Floor, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 ONN, United Kingdom.

The presence of immunoreactive (IR) endothelin, endothelin mRNA, and endothelin receptors in human brain and pituitary gland has been studied by RIA, Northern blot hybridization, and receptor assay. IR endothelin was detected in all five brain regions examined (cerebral cortex, cerebellum, brain stem, basal ganglia, and hypothalamus) (6–10 fmol/g wet wt) and spinal cord (22 ± 6 fmol/g wet wt, n = 7, mean ± SEM). Higher concentrations of IR endothelin were found in the pituitary gland (147 ± 30 fmol/g wet wt). Fast protein liquid chromatographic analysis of the IR endothelin in pituitary gland showed a large IR peak in the position of endothelin-3 and a smaller peak in the position of endothelin-1, whereas IR endothelin in the hypothalamus and brain stem was mainly endothelin-1. Endothelin messenger RNA was detected by Northern blot hybridization in the pituitary but not in hypothalamus. The receptor assay showed that ¹²⁵I-endothelin-1 binding sites were present in large numbers in all five brain regions but were much less abundant in the pituitary gland. Binding capacity and dissociation constant were 5052 ± 740 fmol/mg protein and 0.045 ± 0.007 nM in brain stem and 963 ± 181 fmol/mg protein and 0.034 ± 0.009 nM in hypothalamus. In the pituitary gland, there were two classes of binding sites for endothelin with dissociation constants of 0.059 ± 0.002 nM (binding capacity = 418 ± 63 fmol/mg protein) and 0.652 ± 0.103 nM (binding capacity = 1717 ± 200 fmol/mg protein). Endothelin-1, -2 and -3 were almost equipotent in displacing the binding (IC₅₀ 0.04 nM). These findings are in accord with the possibility that endothelin acts as a neurotransmitter, neuromodulator or neurohormone in man.

Received June 14, 1990.

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