title: Pituitary adenylate cyclase-activating polypeptide 6-38 blocks cocaine- and amphetamine-regulated transcript Peptide-induced hypophagia in rats.
abstract: Cocaine- and amphetamine-regulated transcript peptides (CARTp) suppress nutritional intake after administration into the fourth intracerebral ventricle. Recent in vitro studies have shown that PACAP 6-38, a pituitary adenylate cyclase-activating polypeptide (PACAP) fragment, could act as a competitive antagonist against CARTp 55-102 on a common CARTp-sensitive receptor structure. Here, we show for the first time in vivo that the reduction in solid food intake induced by exogenous CARTp 55-102 (0.3 nmol: 1.5 µg) administered fourth i.c.v. is blocked by pretreatment with PACAP 6-38 (3 nmol). The PACAP 6-38 fragment had no effect by itself either when given into the fourth ventricle or subcutaneously. Although effective to block the CARTp-effect on feeding and short-term body weight, PACAP 6-38 failed to attenuate CARTp-associated gross motor behavioral changes suggesting at least two CARTp-sensitive receptor subtypes. In conclusion, PACAP 6-38 acts as a functional CARTp antagonist in vivo and blocks its effects on feeding and short term weight gain.
authors: Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors: Jonathan R
authors: JR
authors: Burgos
authors: Britt-Marie
authors: BM
authors: Iresjö
authors: Ulrika
authors: U
authors: Smedh
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D005247:Feeding Behavior / Q000187:drug effects; D001068:Feeding and Eating Disorders / Q000188:drug therapy / Q000209:etiology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; C075647:pituitary adenylate-cyclase-activating-peptide (6-38)
references: Synapse. 2008 Feb;62(2):122-7
references: 18000808
references: Nature. 1998 May 7;393(6680):72-6
references: 9590691
references: Am J Physiol Regul Integr Comp Physiol. 2011 Dec;301(6):R1625-34
references: 21957159
references: Peptides. 2007 Oct;28(10):1945-53
references: 17766010
references: Peptides. 2006 Aug;27(8):1926-33
references: 16730858
references: Behav Neurosci. 2002 Oct;116(5):918-21
references: 12369811
references: Gastroenterology. 2010 Apr;138(4):1479-90
references: 19854189
references: J Pharmacol Exp Ther. 2000 Aug;294(2):784-92
references: 10900261
references: J Neurosci. 2001 Oct 1;21(19):7474-80
references: 11567037
references: Hypertension. 2001 Nov;38(5):1096-100
references: 11711504
references: Am J Physiol. 1995 Dec;269(6 Pt 1):G1000-3
references: 8572209
references: Brain Res. 2004 Mar 5;999(2):181-92
references: 14759497
references: Am J Physiol Regul Integr Comp Physiol. 2006 Jul;291(1):R124-30
references: 16455772
references: Synapse. 1998 Aug;29(4):293-8
references: 9661247
references: Int J Obes (Lond). 2011 Jun;35(6):773-84
references: 21060312
references: Neuroscience. 2005;133(3):841-51
references: 15908130
references: Brain Res. 2002 Dec 13;957(2):298-310
references: 12445972
references: Am J Physiol Regul Integr Comp Physiol. 2003 Jun;284(6):R1418-26
references: 12468444
references: J Neurosci. 2009 May 27;29(21):6973-81
references: 19474324
references: Eur J Pharmacol. 2007 Mar 22;559(2-3):109-14
references: 17292884
references: Brain Res. 2001 Mar 2;893(1-2):186-94
references: 11223006
references: Pharmacol Rev. 2009 Sep;61(3):283-357
references: 19805477
references: Peptides. 2006 Jan;27(1):157-64
references: 16154233
references: Neuropeptides. 2011 Oct;45(5):351-8
references: 21855138
references: Brain Res. 1985 Aug 26;341(2):331-6
references: 3899273
references: Am J Physiol Regul Integr Comp Physiol. 2001 Dec;281(6):R1862-7
references: 11705771
references: Peptides. 2006 Jun;27(6):1328-34
references: 16309793
references: Brain Res. 2001 Mar 30;896(1-2):153-6
references: 11277984
references: Endocrinology. 2007 Sep;148(9):4400-10
references: 17569753
references: Am J Physiol Regul Integr Comp Physiol. 2001 Jun;280(6):R1613-9
references: 11353662
references: Endocrinology. 2000 Aug;141(8):2854-60
references: 10919272
references: J Comp Neurol. 1998 Feb 2;391(1):115-32
references: 9527537