Endothelin in human brain and pituitary gland: Presence of immunoreactive endothelin, endothelin messenger ribonucleic acid, and endothelin receptors

Journal Article · Fri Mar 01 04:00:00 EST 1991 · Journal of Clinical Endocrinology and Metabolism; (USA)

DOI:https://doi.org/10.1210/jcem-72-3-693· OSTI ID:5947038

Takahashi, K; Ghatei, M A; Jones, P M; Murphy, J K; Lam, H C; O'Halloran, D J; Bloom, S R ^[1]

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1. Royal Postgraduate Medical School, London (England)

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 approximately 0.04 nM). These findings are in accord with the possibility that endothelin acts as a neurotransmitter, neuromodulator or neurohormone in man.

• OSTI ID: 5947038
• Journal Information: Journal of Clinical Endocrinology and Metabolism; (USA), Journal Name: Journal of Clinical Endocrinology and Metabolism; (USA) Vol. 72:3; ISSN JCEMA; ISSN 0021-972X
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOASSAY
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL LOCALIZATION
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
DIAGNOSTIC TECHNIQUES
DNA HYBRIDIZATION
DRUGS
ENDOCRINE GLANDS
GLANDS
HYBRIDIZATION
IMMUNOASSAY
IMMUNOLOGY
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
MAN
MEMBRANE PROTEINS
MESSENGER-RNA
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PEPTIDES
PITUITARY GLAND
PRIMATES
PROTEINS
RADIOASSAY
RADIOIMMUNOASSAY
RADIOIMMUNODETECTION
RADIOIMMUNOLOGY
RADIORECEPTOR ASSAY
REACTION KINETICS
RECEPTORS
RNA
TRACER TECHNIQUES
VERTEBRATES