The hypothalamus-pituitary-adrenal axis does not influence the protective effects of nociceptin/orphanin FQ on the rat gastric mucosa.
The participation of hypothalamus-pituitary-adrenal axis in the gastroprotective effects of nociceptin/orphanin FQ (N/OFQ) has been investigated. Gastric mucosal lesions were induced by intragastric administration of 50% ethanol, 1 ml/rat. Rats received N/OFQ either by the intracerebroventricular (icv) route, at 3 microg/rat, or by the intraperitoneal (ip) route, at 10 microg/kg, 30 min before ethanol administration. The protective effect of icv and ip administered N/OFQ was assessed in adrenalectomized rats and in rats pretreated with the glucocorticoid receptor antagonist, mifepristone, or with the CRF receptor antagonist, alpha-helical CRF(9-41). The damaging effect of ethanol was apparently not influenced by adrenalectomy. N/OFQ markedly reduced macroscopically and histologically assessed gastric mucosal damage. The extent of reduction by N/OFQ was comparable in adrenalectomized and in sham-operated rats, with either icv or ip route of administration. Pretreatment with mifepristone, both icv (80 microg/rat) and ip (10 mg/kg) injected, did not modify the response to icv and ip N/OFQ. Pretreatment with alpha-helical CRF(9-41) (25 microg/rat icv or 250 microg/kg ip), had no effect on the reduction of gastric damage produced by icv or ip N/OFQ. Present findings suggest that the gastroprotective effects of N/OFQ on ethanol-induced damage do not involve the endocrine pathway through the HPA axis.
Grandi
Daniela
D
Department of Human Anatomy, Pharmacology and Forensic Medicine, University of Parma, Italy.
Solenghi
Elvira
E
Guerrini
Remo
R
Broccardo
Maria
M
Agostini
Simona
S
Petrella
Carla
C
Scaccianoce
Sergio
S
Improta
Giovanna
G
Morini
Giuseppina
G
D000315:Adrenalectomy; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D015735:Mifepristone / Q000008:administration & dosage; D018847:Opioid Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D013272:Stomach Diseases / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D013997:Time Factors; D000097629:Nociceptin
D003346:Corticotropin-Releasing Hormone; D000431:Ethanol; D015735:Mifepristone; D018847:Opioid Peptides; D010446:Peptide Fragments; D011965:Receptors, Glucocorticoid; D000097629:Nociceptin; C045089:corticotropin releasing hormone (9-41)