Central neuropeptide Y receptors are involved in 3rd ventricular ghrelin induced alteration of colonic transit time in conscious fed rats.
BACKGROUND
Feeding related peptides have been shown to be additionally involved in the central autonomic control of gastrointestinal functions. Recent studies have shown that ghrelin, a stomach-derived orexigenic peptide, is involved in the autonomic regulation of GI function besides feeding behavior. Pharmacological evidence indicates that ghrelin effects on food intake are mediated by neuropeptide Y in the central nervous system.


METHODS
In the present study we examine the role of ghrelin in the central autonomic control of GI motility using intracerobroventricular and IP microinjections in a freely moving conscious rat model. Further the hypothesis that a functional relationship between NPY and ghrelin within the CNS exists was addressed.


RESULTS
ICV injections of ghrelin (0.03 nmol, 0.3 nmol and 3.0 nmol/5 microl and saline controls) decreased the colonic transit time up to 43%. IP injections of ghrelin (0.3 nmol - 3.0 nmol kg(-1) BW and saline controls) decreased colonic transit time dose related. Central administration of the NPY1 receptor antagonist, BIBP-3226, prior to centrally or peripherally administration of ghrelin antagonized the ghrelin induced stimulation of colonic transit. On the contrary ICV-pretreatment with the NPY2 receptor antagonist, BIIE-0246, failed to modulate the ghrelin induced stimulation of colonic motility.


CONCLUSIONS
The results suggest that ghrelin acts in the central nervous system to modulate gastrointestinal motor function utilizing NPY1 receptor dependent mechanisms.
Tebbe
Johannes J
JJ
Department of Internal Medicine, Division Gastroenterology - Endocrinology, Philipps Universität Marburg, 35033 Marburg, Germany. tebbe@staff.uni.marburg.de
Tebbe
Clemens G
CG
Mronga
Silke
S
Ritter
Michael
M
Schäfer
Martin K H
MK
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D003106:Colon / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000187:drug effects; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology*; D054439:Ghrelin; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D036361:Peptide Hormones / Q000008:administration & dosage / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000502:physiology*; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors / Q000502:physiology*; D017476:Receptors, Neuropeptide Y / Q000502:physiology; D020542:Third Ventricle / Q000378:metabolism*
C092926:BIBP 3226; D054439:Ghrelin; C066211:Npy1r protein, rat; D036361:Peptide Hormones; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D001120:Arginine
Neurogastroenterol Motil. 2000 Aug;12(4):343-52
10886676
Biochem Biophys Res Commun. 2000 Oct 5;276(3):905-8
11027567
Endocrinology. 2000 Nov;141(11):4255-61
11089560
J Med Chem. 2000 Nov 16;43(23):4370-6
11087562
Nature. 2001 Jan 11;409(6817):194-8
11196643
Diabetes. 2001 Feb;50(2):227-32
11272130
Biochem Biophys Res Commun. 2001 Jan 26;280(3):904-7
11162609
Gastroenterology. 2001 Feb;120(2):337-45
11159873
Nat Rev Neurosci. 2001 Aug;2(8):551-60
11483998
Diabetes. 2001 Nov;50(11):2438-43
11679419
Peptides. 2001 Dec;22(12):2055-9
11786190
Neuropsychopharmacology. 2002 May;26(5):615-24
11927186
Am J Physiol Gastrointest Liver Physiol. 2002 Jun;282(6):G948-52
12016119
Neurosci Lett. 2002 May 31;325(1):47-51
12023064
J Pharmacol Exp Ther. 2002 Aug;302(2):822-7
12130749
Endocrinology. 2002 Sep;143(9):3268-75
12193538
Diabetes. 2002 Dec;51(12):3412-9
12453894
Endocrinology. 2003 Feb;144(2):544-51
12538615
Neuron. 2003 Feb 20;37(4):649-61
12597862
J Physiol. 2003 Jul 1;550(Pt 1):227-40
12837928
Peptides. 2003 Jun;24(6):919-23
12948845
Am J Physiol Gastrointest Liver Physiol. 2003 Dec;285(6):G1075-83
12855401
Peptides. 2003 Dec;24(12):1921-8
15127943
Endocrinology. 2004 Jun;145(6):2607-12
14962995
Regul Pept. 1986 Feb;13(3-4):307-18
3010387
Br J Pharmacol. 1991 Jan;102(1):41-4
1646061
Eur J Pharmacol. 1994 Dec 27;271(2-3):R11-3
7705422
Neuroendocrinology. 1999 Nov;70(5):306-16
10567856
Nature. 1999 Dec 9;402(6762):656-60
10604470
Eur J Pharmacol. 1999 Nov 19;384(2-3):R3-5
10611450
Am J Physiol Gastrointest Liver Physiol. 2000 Jan;278(1):G32-8
10644559