title: Insulin-like peptide 5: expression in the mouse brain and mobilization of calcium.
abstract: Insulin-like peptide 5 (INSL5) mRNA was detected in the mouse hypothalamus by RT-PCR. Immunohistochemical studies using an antiserum against the mouse INSL5 peptide revealed INSL5-immunoreactive (irINSL5) neurons in the paraventricular, supraoptic, accessory secretory, and supraoptic retrochiasmatic nuclei and immunoreactive cell processes in the internal layer of the median eminence. In the pituitary, irINSL5 was detected in terminal-like elements of the posterior lobe and in cells of the anterior lobe. Double-labeling experiments showed that irINSL5 is expressed in vasopressin-, but not oxytocin-containing neurons. INSL5 (100 nm) administered to dissociated and cultured mouse hypothalamic neurons elevated cytosolic calcium concentrations [Ca(2+)](i), as assessed by the microfluorimetric fura-2 method. In a Ca(2+)-free medium, INSL5 induced in dissociated neurons an increase of [Ca(2+)](i), which was sensitive to the endoplasmic reticulum calcium pump inhibitor thapsigargin (1 microm) and the IP(3) receptor blocker 2-aminoethoxydiphenyl borate (100 microm) or xestospongin C (5 microm). Our result provides the first evidence that INSL5 is expressed in a population of cells in the mouse hypothalamus and pituitary and that it elevates [Ca(2+)](i) by a mechanism involving both Ca(2+) influx and Ca(2+) release from intracellular stores. The concentration of irINSL5 in the hypothalamic-pituitary axis suggests a neuroendocrine function of this insulin superfamily member.
authors.affiliation: Department of Pharmacology, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Siok L
authors.initials: SL
authors.lastname: Dun
authors.forename: Eugen
authors.initials: E
authors.lastname: Brailoiu
authors.forename: Yulin
authors.initials: Y
authors.lastname: Wang
authors.forename: G Cristina
authors.initials: GC
authors.lastname: Brailoiu
authors.forename: Lee-Yuan
authors.initials: LY
authors.lastname: Liu-Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Jaw Kang
authors.initials: JK
authors.lastname: Chang
authors.forename: Nae J
authors.initials: NJ
authors.lastname: Dun
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007328:Insulin / Q000096:biosynthesis*; D051379:Mice; D008813:Mice, Inbred ICR; D018613:Microscopy, Confocal; D009474:Neurons / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism; D011506:Proteins; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins; D012333:RNA, Messenger; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium