主催: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
会議名: WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
開催地: Kyoto
開催日: 2018/07/01 - 2018/07/06
Introduction. Nesfatin-1 is a recently discovered 82-amino acid peptide derived from nucleobindin2 (NUCB2). NUCB2/nesfatin-1 is widely distributed in brain areas involved in the regulation of feeding, emotion and emesis.
Aims. In the present studies, we identified the amino acid sequence of nesfatin-1 in Suncus murinus (SM). We investigated the action of nesfatin-1 to affect locomotor activity, feeding and emesis, and gastrointestinal contractility.
Methods. The amino acid sequence of SM nesfatin-1 was determined using in silico cloning. In in vivo studies, nesfatin-1 (1-50 pmol, i.c.v.) or saline (5 µl, i.c.v.) was administered to conscious animals after an overnight fast. Emesis and spontaneous behaviour were measured for 6 h, while food and water consumption was measured hourly for 6 h and at 24 h post-administration. The potential action of nesfatin-1 on the ileum was investigated in vitro using an isolated organ bath setup.
Results. The amino acid sequence of SM nesfatin-1 showed high homology with humans, rats and mice (86.6% to humans and rats; 85.4% to mice). The administration of nesfatin-1 at 5 pmol, i.c.v., suppressed cumulative food intake at 4 to 6 h (～30% reduction compared to controls; P<0.01; cumulative measurements), without affecting the latency to eat (P>0.05). Nesfatin-1 at 1 pmol, i.c.v. suppressed cumulative water intake assessed at 5 h (P<0.05). Nesfatin-1 at 25 pmol, i.c.v. suppressed cumulative food and water intake at 24 h by 28.3% and 35.4%, respectively (P<0.01). In addition, nesfatin-1 at 5 pmol, i.c.v. induced emesis in 5 out of 6 animals (18.8 ± 8.3 retches and 4.7 ± 2.1 vomits; P<0.05), following a median latency of 40 min (P<0.05). Nesfatin-1 had no effect on locomotor activity and also failed to contract or relax the isolated ileum.
Conclusions. Nesfatin-1 is highly conserved in SM, humans, rats and mice. To the best of our knowledge, nesfatin-1 is the most potent peptide to induce emesis and inhibit feeding in SM. The studies were fully supported by a grant from the Research Grants Council of the Hong Kong SAR, China (Project no. UGC/FDS11/M02/16).
