title: Intermedin 17-47 does not function as a full intermedin antagonist within the central nervous system or pituitary.
abstract: A fragment of intermedin (IMD), IMD17-47, has been shown to antagonize the hypotensive effects of intravenous IMD administration; however, the effects of IMD17-47 have not been studied in other systems such as brain and pituitary gland. IMD17-47 was administered intracerebroventricularly (i.c.v.) into male rats alone or prior to administration of IMD; and blood pressure and food and water intakes measured. Multiple doses of IMD17-47 failed to alter basal blood pressure and heart rate, but did partially reverse the stimulatory effects of IMD given i.c.v. on blood pressure and heart rate. A low dose of IMD17-47 by itself significantly increased basal food and water intake. However, a higher dose of the antagonist did not alter food or water intake compared to control treated rats. No dose of IMD17-47 was able to reverse the inhibitory effects of IMD administered i.c.v. on food and water intake. Furthermore, IMD17-47 failed to significantly alter the inhibitory effects of IMD on growth hormone releasing hormone-stimulated growth hormone release from dispersed anterior pituitary cells in culture. A siRNA molecule designed to compromise IMD production was able to reduce brain IMD levels and did, upon i.c.v. administration, cause increased water drinking in male rats. This tool may provide a better method than the use of the IMD17-47 compound to study the role of endogenous IMD within the CNS and pituitary.
authors.affiliation: Saint Louis University, School of Medicine, Department of Pharmacological and Physiological Science, 1402 S. Grand Boulevard, St. Louis, MO 63104, USA. mwhite44@slu.edu
authors.forename: Meghan M
authors.initials: MM
authors.lastname: White
authors.forename: Willis K
authors.initials: WK
authors.lastname: Samson
mesh_terms: D053607:Adrenomedullin / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002460:Cell Line; D002490:Central Nervous System / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D013006:Growth Hormone / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007276:Injections, Intraventricular; D008297:Male; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C499411:Adm2 protein, rat; D009479:Neuropeptides; D010446:Peptide Fragments; D053607:Adrenomedullin; D013006:Growth Hormone