ArticlesMouse pancreatic polypeptide modulates food intake, while not influencing anxiety in mice☆☆
Introduction
Pancreatic polypeptide (PP) is a 36-amino acid peptide that belongs to a family of peptides that includes neuropeptide Y (NPY) and peptide YY (PYY). PP is produced in PP cells of pancreatic islets of Langerhans and released into circulation after ingestion of food [1]. PP exerts a variety of regulatory actions, including inhibition of pancreatic exocrine secretion, gallbladder contraction, stimulation of glucocorticoid secretion, modulation of gastric acid secretion, and gastrointestinal motility [7]. Besides these, PP may have some unknown role in other tissues in which PP-binding sites were observed, including the brain, prostate, and liver [16], [20]. PP receptor in the brain has been suggested on the basis of radioreceptor assay [20], mRNA expression by Northern analysis [2] and receptor autoradiography [21]. Furthermore, PP mRNA within the brain was identified by Reverse-transcriptase PCR [21].
The PP family of three peptides shares a characteristic structure consisting of a type prolyl/prolyl helix followed by a β turn and an α helical region [3]. NPY and PYY exhibit 70% homology with each other and about 50% with PP [13]. In this family PP is noteworthy for being the least conserved across species. Mouse PP differs from rat PP at residues 43 (His→Pro) and 46 (Arg→Met) and from that of human PP at residues 35 (Val→Met), 40 (Asn→Tyr), 50 (Ala→Glu), 51 (Ala→Thr), 52 (Asp→Gln), and 59 (Met→Thr) [24]. In addition, the ovine, porcine, canine, and bovine peptides have also been sequenced. However, the physiological role of PP still remains to be determined. Therefore, taking species differences in PP into consideration, we used synthetic mouse PP to investigate the detailed effects of PP on food intake and anxiety in mice.
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Materials and methods
Mouse PP was custom synthesized by Sawady Technology (Tokyo, Japan). This peptide was diluted in 4 μl of artificial cerebrospinal fluid (ACSF), which also served as the control solution, and was injected intracerebroventricularly (ICV) at doses of 0.003–3 nmol. For intraperitoneal (IP) injection, mouse PP was diluted in 100 μl of physiological saline, which also served as the control solution, and was injected at IP doses of 0.03–30 nmol.
Male mice (32–35 g) of the ddy strain (JAPAN SLC Inc.,
Results
The effect of ICV injection of mouse PP on food intake in non-food-deprived mice is shown in Fig. 1. Mouse PP injected ICV increased cumulative food intake compared to ACSF-treated controls. Cumulative food intake was significantly increased by 0.3 nmol at 20 min (0.120 ± 0.032 vs. 0.045 ± 0.015 g (control), P < 0.029), 1 h (0.212 ± 0.049 vs. 0.095 ± 0.027 g (control), P < 0.033), 2 h (0.305 ± 0.056 vs. 0.141 ± 0.033 g (control), P < 0.015) and 4 h (0.525 ± 0.083 vs. 0.324 ± 0.061 g (control),
Discussion
In this study ICV injection of mouse PP increased food intake. On the other hand, IP injection of mouse PP decreased food intake. To examine more detailed functions of PP, we administered custom synthetic mouse PP to the mice, focusing attention on species specificity’s in the response of PP. This is the first report about the effects of mouse PP on feeding in mice.
Central mechanisms regulating feeding behavior are complex and still remain to be determined [11]. It is widely acknowledged that
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☆ This work was supported in part by Grants-in-Aid for Scientific Research (A) 08559012 and (C) 09671057 from The Ministry of Education, Science and Culture of Japan (to A.I.).