title: Receptors and neurosecretory actions of endothelin in hypothalamic neurons.
abstract: Primary cultures of rat hypothalamic neurons were found to secrete the potent calcium-mobilizing and mitogenic peptide endothelin (ET) and to contain specific ET binding sites with higher affinity for ET-1 and ET-2 than ET-3. ET receptors of similar specificity were also identified in two gonadotropin-releasing hormone (GnRH) neuronal cell lines (GT1-1 and GT1-7). In both primary cultures and GnRH neurons, receptor binding of ETs led to marked and dose-dependent increases of inositol phosphates; inositol bis-, tris-, and tetrakisphosphates increased promptly, reached a peak within 2 min, and returned toward the steady-state levels during the next 10 min. ET-1 was more potent than ET-3 in mobilizing inositol phosphates, consistent with its greater affinity for the ET receptors in these cells. ET also stimulated GnRH secretion from perifused hypothalamic cultures and GnRH cell lines, with a sharp increase followed by a prompt decline to the basal level. These data show that ET is produced in the hypothalamus and acts through calcium-mobilizing ET receptors in normal and transformed secretory neurons to stimulate GnRH release. These actions of locally produced ETs upon GnRH-secreting neurons indicate that the vasoconstrictor peptides have the capacity to regulate neurosecretion and could participate in the hypothalamic control of anterior pituitary function and gonadotropin secretion.
authors.affiliation: Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
authors.forename: L Z
authors.initials: LZ
authors.lastname: Krsmanović
authors.forename: S S
authors.initials: SS
authors.lastname: Stojilković
authors.forename: T
authors.initials: T
authors.lastname: Balla
authors.forename: S
authors.initials: S
authors.lastname: al-Damluji
authors.forename: R I
authors.initials: RI
authors.lastname: Weiner
authors.forename: K J
authors.initials: KJ
authors.lastname: Catt
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology*; D005333:Fetus; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000502:physiology*; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D009474:Neurons / Q000502:physiology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D017466:Receptors, Endothelin
chemical_list: D016232:Endothelins; D007295:Inositol Phosphates; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D007987:Gonadotropin-Releasing Hormone