title: Intravenous injection of urocortin 1 induces a CRF2 mediated increase in circulating ghrelin and glucose levels through distinct mechanisms in rats.
abstract: Urocortins (Ucns) injected peripherally decrease food intake and gastric emptying through peripheral CRF(2) receptors in rodents. However, whether Ucns influence circulating levels of the orexigenic and prokinetic hormone, ghrelin has been little investigated. We examined plasma levels of ghrelin and blood glucose after intravenous (iv) injection of Ucn 1, the CRF receptor subtype involved and underlying mechanisms in ad libitum fed rats equipped with a chronic iv cannula. Ucn 1 (10 μg/kg, iv) induced a rapid onset and long lasting increase in ghrelin levels reaching 68% and 219% at 0.5 and 3h post injection respectively and a 5-h hyperglycemic response. The selective CRF(2) agonist, Ucn 2 (3 μg/kg, iv) increased fasting acyl (3h: 49%) and des-acyl ghrelin levels (3h: 30%) compared to vehicle while the preferential CRF(1) agonist, CRF (3 μg/kg, iv) had no effect. Ucn 1's stimulatory actions were blocked by the selective CRF(2) antagonist, astressin(2)-B (100 μg/kg, iv). Hexamethonium (10 mg/kg, sc) prevented Ucn 1-induced rise in total ghrelin levels while not altering the hyperglycemic response. These data indicate that systemic injection of Ucns induces a CRF(2)-mediated increase in circulating ghrelin levels likely via indirect actions on gastric ghrelin cells that involves a nicotinic pathway independently from the hyperglycemic response.
authors.affiliation: CURE/Digestive Diseases Research Center and Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division at University of California Los Angeles, Los Angeles, CA 90073, USA. lixinw@ucla.edu
authors.forename: Lixin
authors.initials: L
authors.lastname: Wang
authors.forename: Andreas
authors.initials: A
authors.lastname: Stengel
authors.forename: Miriam
authors.initials: M
authors.lastname: Goebel-Stengel
authors.forename: Almaas
authors.initials: A
authors.lastname: Shaikh
authors.forename: Pu-Qing
authors.initials: PQ
authors.lastname: Yuan
authors.forename: Yvette
authors.initials: Y
authors.lastname: Taché
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology; D001786:Blood Glucose; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology / Q000502:physiology; D054439:Ghrelin / Q000097:blood*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054832:Urocortins / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*
chemical_list: D001786:Blood Glucose; C101531:CRF receptor type 2; D054439:Ghrelin; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D018019:Receptors, Corticotropin-Releasing Hormone; C426705:UCN2 protein, human; D054832:Urocortins; C528574:astressin-2B; D003346:Corticotropin-Releasing Hormone