ABSTRACT
Title
Central NeuropeptideS inhibits stress-stimulated defecation in the rat
Authors
C. Petrella1, S. Agostini2, G. Calò3, A. Giaquinto1, C. De Nuccio4, G. Improta1 and M. Broccardo1.
1Dept. of Physiology and Pharmacology “V. Erspamer” University Sapienza Rome, Italy; 2INRA, Toulouse, France 3Dept. of Experimental and Clinical Medicine, Section of Pharmacology and Neuroscience Center, University of Ferrara Italy; 4Dept. of Cell Biology and Neurosciences, Section of Degenerative and Inflammatory Neurological Diseases, Istituto Superiore di Sanita', Rome,Italy
Abstract
Neuropeptide S (NPS) is a bioactive peptide recently identified that activates an orphan G-protein coupled receptor, named NPS receptor (NPSR). In rats, NPS and NPSR constitute a novel neuropeptide system expressed in both central nervous system and peripheral tissues, controlling visceromotor, neuroendocrine, pain and behavioural responses To improve the still poor knowledge of the role of NPS-NPSR system in the gastrointestinal (GI) tract , we investigated 1) the supraspinal effect of NPS on motor functions of upper (gastric emptying and gastrointestinal transit)- and lower (distal colonic transit)- GI tract in basal conditions and during pathological states (restraint stress- and CRF-induced defecation) in the rat, and 2) the underlying receptor mechanisms by using pretreatment with NPS (D-Cys(tBu)5]NPS) -, NK3 TK(SR142801)- and opioid (naloxone)-receptor antagonists. Intracerebroventricular injection of NPS which failed to modify basal gastric emptying, gastrointestinal transit and distal colon propulsion, significantly and dose-dependently (0.5 – 4 nmol/rat) reduced the faecal pellet excretion and weight stimulated by restraint stress and CRF. NPS inhibitory effect on stress-induce defecation was unmodified by pretreatment with both TK- and opioid -receptor antagonists and was partially abolished by NPSR antagonist.
The present study demonstrated, for the first time, that supraspinal NPS system which does not participate in the physiological control of GI motility, conversely, plays an inhibitory role on defecation stimulated by restraint stress and CRF. The combination of the NPS ability to inhibit faecal output together with its yet known anxiolytic effect is particularly promising especiallyin those pathological conditions as IBS, where the stress and the hyperactivity of the CRF system contribute to the co-morbidity of anxiety with colonic motor symptoms as diarrhoea.
The present study demonstrated, for the first time, that supraspinal NPS system which does not participate in the physiological control of GI motility, conversely, plays an inhibitory role on defecation stimulated by restraint stress and CRF. The combination of the NPS ability to inhibit faecal output together with its yet known anxiolytic effect is particularly promising especiallyin those pathological conditions as IBS, where the stress and the hyperactivity of the CRF system contribute to the co-morbidity of anxiety with colonic motor symptoms as diarrhoea.