This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Dun, S. L. Articles by Dun, N. J. Search for Related Content PubMed PubMed Citation Articles by Dun, S. L. Articles by Dun, N. J.

Insulin-Like Peptide 5: Expression in the Mouse Brain and Mobilization of Calcium

Department of Pharmacology (S.L.D., E.B., Y.W., G.C.B., L.-Y.L.-C., N.J.D.), Temple University School of Medicine, Philadelphia, Pennsylvania 19140; and Phoenix Pharmaceuticals Inc. (J.Y., J.K.C.), Belmont, California 94002

Address all correspondence and requests for reprints to: Nae J. Dun, Department of Pharmacology, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, Pennsylvania 19140. E-mail: ndun{at}temple.edu.

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 [Ca²⁺]_i, as assessed by the microfluorimetric fura-2 method. In a Ca²⁺-free medium, INSL5 induced in dissociated neurons an increase of [Ca²⁺]_i, which was sensitive to the endoplasmic reticulum calcium pump inhibitor thapsigargin (1 µM) and the IP₃ receptor blocker 2-aminoethoxydiphenyl borate (100 µM) or xestospongin C (5 µM). 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 [Ca²⁺]_i by a mechanism involving both Ca²⁺ influx and Ca²⁺ release from intracellular stores. The concentration of irINSL5 in the hypothalamic-pituitary axis suggests a neuroendocrine function of this insulin superfamily member.