Nociceptin/orphanin FQ-induced delay in gastric emptying: role of central corticotropin-releasing factor and glucocorticoid receptors.
When injected intracerebroventricularly (i.c.v.) in rats, nociceptin/orphanin FQ (N/OFQ) delays gastric emptying and increases plasma corticosterone levels. Our aim in this study was to investigate changes in gastric emptying of a phenol red meal, and the plasma corticosterone response to N/OFQ in adrenalectomized (ADX) rats, in ADX rats injected with corticosterone at 1, 24 and 72 h before the gastric emptying assay, and in intact rats i.c.v. pretreated with a glucocorticoid antagonist (RU486) and with a corticotropin-releasing factor receptor antagonist (alpha-helical CRF9-41). In adrenal intact rats, i.c.v. injection of N/OFQ (2.5 nmol rat-1) significantly delayed gastric emptying (by 70%) and increased plasma corticosterone concentrations. Conversely, in ADX rats, N/OFQ left gastric emptying unchanged. In ADX rats, corticosterone injected at 1, 24 and 72 h before the gastric emptying assay almost restored the N/OFQ-induced delay in gastric emptying. Finally, pretreatment with RU486- and alpha-helical CRF9-41 abolished the N/OFQ-induced inhibition of gastric emptying. These findings suggest that central N/OFQ inhibits gastric emptying through an integrated orphaninergic system-CRF interaction in which corticosterone plays a permissive role.
Broccardo
M
M
Department of Human Physiology and Pharmacology V. Erspamer, University of Rome La Sapienza, Rome, Italy. maria.borccardo@uniroma1.it
Scaccianoce
S
S
Del Bianco
P
P
Agostini
S
S
Petrella
C
C
Improta
G
G
D000315:Adrenalectomy; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000494:pharmacology; D004396:Coloring Agents; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D005746:Gastric Emptying / Q000187:drug effects*; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D015735:Mifepristone / Q000008:administration & dosage / Q000494:pharmacology; D018847:Opioid Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D010637:Phenolsulfonphthalein; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000187:drug effects*; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000187:drug effects*; D000097629:Nociceptin
D000893:Anti-Inflammatory Agents; D004396:Coloring Agents; D003345:Corticosterone; D003346:Corticotropin-Releasing Hormone; D006727:Hormone Antagonists; D015735:Mifepristone; D018847:Opioid Peptides; D010446:Peptide Fragments; D010637:Phenolsulfonphthalein; D018019:Receptors, Corticotropin-Releasing Hormone; D011965:Receptors, Glucocorticoid; D000097629:Nociceptin; C045089:corticotropin releasing hormone (9-41)