Primaty cultures of rat hypothal c neurons were found. to secrete the potent calcium mobiling ad mitogenic peptide Idotbol (EI) and to contain specific ET binding sites with higher t for ET-1 and ET-2 thautET-3.ET receptors of simlor were also idetfiedin two gonadotropln-releasn hormone (GnRH) neuronal ce line (GT1-1 and GT1-7). In both pry cultures and GnRH neurons, receptor bnding Of ETs led to marked and dosedependent increases of inositol phosphates; inositol bis-, this-, and tetakisphosphates increased promptly, reached a peak withlN 2 min, and retured toward the steady-state levels during the next 10 min. ET-1 was more potent than (8,9). ETA receptors have higher affinity for ET-L and ET-2 than for ET-3, whereas ETB receptors do not discriminate between the three ETs.ETs have a wide spectrum of pharmacological effects at locations other than blood vessels (5-7), and receptors specific for ET-1 and ET-2 or for ET-3 are present in several tissues including the intestine, heart, lungs, kidney, adrenal gland, pituitary, and brain (10)(11)(12)(13)(14)(15)