ENDOTHELIN IN HUMAN BRAIN AND PITUITARY-GLAND - COMPARISON WITH RAT

To investigate the physiological roles of endothelin (ET) in the brain and pituitary gland, the presence of immunoreactive (ir) ET and ET receptors was studied by radioimmunoassay and receptor assay in humans and rats. ir-ET concentrations in human brain (6-10 fmol/g of wet weight) were comparable with the levels in the rat brain (5-9 fmol/g of wet weight). Higher concentrations of ir-ET were found in human pituitary glands (147 +/- 30 fmol/g of wet weight, mean +/- SEM) and rat posterior pituitary lobes (88 +/- 26 fmol/g of wet weight). Fast protein liquid chromatography (FPLC) showed that the ir-ET in human hypothalamus and brainstem was mainly ET-1, while the ir-ET in human pituitary was mainly ET-3. FPLC of the whole rat brain extract showed a larger peak in the position of ET-3 and a smaller peak in the position of ET-1. Receptor assay showed that [I-125]ET-1 binding sites were present in very numbers in all five human brain regions and four rat brain regions examined but were much less abundant in the human pituitary. ET mRNA was detected by Northern blot hybridization in human pituitary but not in human hypothalamus. These findings are in accord with the possibility that ET acts as a neurotransmitter, neuromodulator, or neurohormone.