ISSN:
1432-2072
Keywords:
Key words Nociceptin
;
Orphanin FQ
;
Food intake
;
Food deprivation
;
Neuropeptide Y
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Rationale: Central injections of nociceptin (NC) stimulate feeding in rats. Objective: The present study evaluated the effect of N-terminal partial sequences or analogues of NC on food intake in male Wistar rats, to characterize pharmacologically the NC receptor mediating the hyperphagic effect. Methods: NC and related peptides were injected into the lateral (LV) or third (3V) cerebroventricle in freely feeding rats. Results: In the LV, NC stimulated feeding. The N-terminal fragment NC(1–13)NH2 proved to be the least active sequence with hyperphagic activity; NC(1–12)NH2 and NC(1–9)NH2 were inactive. [Phe1ψ(CH2-NH)Gly2]NC(1–13)NH2 ([F/G)]NC(1–13)NH2), an analogue of NC(1–13)NH2, markedly stimulated feeding and, coadministered in the LV with NC, never reduced the hyperphagic effect of the natural sequence. These findings suggest that [F/G)]NC(1–13)NH2, which has been reported to act as a NC receptor antagonist in peripheral tissues, be- haves as a full agonist at the central NC receptors controlling feeding. The hyperphagic potencies of NC and [F/G)]NC(1–13)NH2 were much higher following injection into the 3V than in the LV. Another analogue of NC(1–13)NH2, namely [Nphe1]NC(1–13)NH2, injected into the 3V did not stimulate feeding, but reduced the effect of NC. [Nphe1]NC(1–13)NH2 at a dose of 16.8 nmol/rat significantly reduced, and at 168 nmol/rat almost completely abolished the effect of NC (1.68 nmol/rat). The latter dose of [Nphe1]NC(1–13)NH2 significantly reduced also feeding induced by food deprivation, but did not modify the hyperphagic effect of neuropeptide Y (0.3 nmol/rat). Conclusions: The present results confirm the orexigenic effect of NC in freely feeding rats and indicate that [Nphe1]NC(1–13)NH2 may represent a selective NC receptor antagonist to study the physiological and pathophysiological role of NC in feeding behaviour.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002130050073
Permalink
