Peripheral infusion of nociceptin/orphanin FQ influences the response of rat gastric and colonic mucosa to repeated stress.
The 17-amino acid peptide nociceptin/orphanin FQ (N/OFQ) plays a role in the regulation of stress responses and of emotional disorders. The objective of this study is to evaluate whether long-term peripheral N/OFQ could dose- and time-dependently influence the responses to repeated cold-restraint stress on the rat gastric and colonic mucosa. Rats were exposed to cold-restraint stress for 3h per day for 1, 2 and 3 consecutive days. N/OFQ was administered at doses of 0.1, 1 and 10 microg/kg/h via Alzet osmotic minipumps. In the gastric fundus, N/OFQ exerted dose-dependent beneficial effects against acute and repeated stress but, after prolonged treatment, became damaging in non-stressed rats. In the distal colon, N/OFQ exerted a protective effect against damage by acute and repeated stress with no influence on epithelial integrity in non-stressed rats. In both regions, the peptide itself dose- and time-dependently reduced intraepithelial mucins. The reduction in mucin content caused by stress was effectively counteracted by N/OFQ, 0.1 microg/kg/h, in the distal colon only. N/OFQ did not modify basal mucosal cell proliferation. The peptide at 0.1 and 1 microg/kg/h had no influence while at 10 microg/kg/h abolished stress-induced increase in cell proliferation. The present results provide evidence that N/OFQ is implicated in the regulation of resting and stress-challenged mucosal integrity and activity of mucin-producing cells.
Grandi
Daniela
D
Department of Human Anatomy, Pharmacology and Forensic Medicine, University of Parma, Parma, Italy.
Solenghi
Elvira
E
Massi
Maurizio
M
Morini
Giuseppina
G
D000818:Animals; D003106:Colon / Q000187:drug effects*; D005508:Food Deprivation; D005753:Gastric Mucosa / Q000187:drug effects*; D007150:Immunohistochemistry; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D007413:Intestinal Mucosa / Q000187:drug effects*; D008297:Male; D008855:Microscopy, Electron, Scanning; D018847:Opioid Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*; D000097629:Nociceptin
D018847:Opioid Peptides; D014665:Vasodilator Agents; D000097629:Nociceptin