Localization of peptide YY (PYY) in gastrointestinal endocrine cells and effects on intestinal blood flow and motility.

Abstract

In immunohistochemical studies using antisera to peptide YY (PYY), a 36 amino acid polypeptide isolated from porcine duodenum, it was found that PYY-like immunoreactivity occurred mainly in endocrine cells of the gastrointestinal mucosa. PYY-immunoreactive cells were particularly abundant in the distal intestine and have been observed in five species, including man. By radioimmunoassay it was found that, in the rat, the amount of PYY immunoreactivity was about 100-fold higher in the colon than in the duodenum. The chromatographic profiles of PYY immunoreactivity from the rat colon and porcine PYY on a SP-Sephadex ion exchanger were similar. Furthermore, serial dilutions of extracts from the rat colon and porcine PYY had parallel displacement curves in radioimmunoassay. Close intraartei..d administration of PYY in cats caused an intestinal vasoconstriction and an inhibition ofjejunal and colonic motility. Simultaneously there was a rise in systemic arterial blood pressure. These effects of PYY were also observed after pretreatment with adrenergic blocking agents. It is concluded that PYY is a gastrointestinal peptide that is present mainly in endocrine cells of distal intestine and that has effects on both intestinal motility and the cardiovascular system. Pancreatic polypeptides (PPs) of 36 amino acids have been isolated from the pancreata of several species (1-3). Immunohistochemical studies suggest that a PP-like substance is also present in neurons (4,5). Recently a peptide with structural similarities to PP, peptide YY [PYY, the peptide (P) having NH2-terminal tyrosine (Y) and COOH-terminal tyrosine (Y) amide], has been isolated from porcine duodenum by making use ofan assay for its COOH-terminal tyrosine amide structure (6,7). In the present communication we report on the cellular localization of PYY, measurements and characterization using radioimmunoassay, and some of its effects on gastrointestinal functions. The results indicate that PYY is localized in gut endocrine cells of several species, including man, particularly in middle and distal intestine. Furthermore, PYY has a vasoconstrictor action and inhibits jejunal and colonic motility. We therefore propose that PYY is a gastrointestinal peptide with paracrine or hormonal actions. MATERIALS AND METHODSPYY isolated from porcine duodenum was used (6). Antisera to PYY were produced in rabbits by using a direct immunization procedure. PYY (50-100 ,g) was emulsified with Freund's adjuvant and injected intradermally at multiple sites. Booster doses were given subcutaneously at 2-week intervals for 2 months.PYY was labeled with "2I to a high specific activity (about The publication costs ofthis article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement' in accordance with 18 U. S. C. §1734 solely to indicate this fact. 4471200 Ci/mmol; 1 Ci = 3.7 X 1010 becquerels) by using the chloramine-T method (8). The peptide was separated from free iodine by chromatography on a small Sephadex G-25 col...

PYY transgenic mice are protected against diet-induced and genetic obesity

“…However, although TRH levels were significantly reduced by high-fat feeding in wild type animals, TRH levels in PYY transgenic animals were unaffected by diet and were significantly higher in high-fat fed PYYtg mice compared with high-fat fed wild types ( Table 2). alpha cells in the islets of Langerhan, known to produce PYY (Lundberg et al, 1982), clearly demonstrated that under conditions of high-fat feeding, the number of PYY-positive alpha cells in the islets of Langerhans was significantly higher in PYY transgenic mice compared to wild type mice (Table 1). In this regard it is noteworthy that high-fat feeding increases alpha cell size, volume and number (Cerf et al, 2005).…”

“…Serum concentrations of PYY were elevated in fat-fed transgenic mice (40.6 ± 5.9 pM versus 24.4 ± 2.8 pM in fat-fed wild types, means ± SEM of 3-5 mice per group), albeit this difference did not reach statistical significance. Nevertheless, quantification of alpha cells in the islets of Langerhan, known to produce PYY (Lundberg et al, 1982), clearly demonstrated that under conditions of high-fat feeding, the number of PYY-positive alpha cells in the islets of Langerhans was significantly higher in PYY transgenic mice compared to wild type mice (Table 1). In this regard it is noteworthy that high-fat feeding increases alpha cell size, volume and number (Cerf et al, 2005).…”

“…Two forms of PYY exist in the circulation: the full length PYY1-36, and the shortened form PYY3-36, cleaved from secreted PYY1-36 by the cell surface enzyme dipeptidyl peptidase IV (Lundberg et al, 1982). PYY1-36 binds to all known Y receptors, albeit to each with differing affinities, whereas PYY3-36 preferentially binds the Y2 receptor and to a lesser extent the Y5 receptor (Blomqvist and Herzog, 1997).…”

The role of peptide YY in regulating glucose homeostasis

“…These include inhibiting glucose-stimulated insulin secretion [12], inhibiting gastric secretion and emptying [3], decreasing gastrointestinal motility [29], reducing gallbladder emptying [23], inhibiting pancreatic and intestinal secretion [46], promoting vasoconstriction to the gastrointestinal tract and pancreas [30] and [46] and enhancing salt and water absorption in the colon [39]. All of these PYY-mediated effects are induced via actions on the brainstem, and could affect digestion, absorption, satiety and energy balance [37] and [40].…”

Isolation and characterization of neuropeptide Y from porcine intestine

“…PYY is confined in the endocrine cells of intestine. This peptide also causes a potent colonic vasoconstriction and inhibition of colonic motility [22]. PYY may thus exert its actions via an endocrine route.…”