peptide-yy and Fistula

Peptide YY (PYY) is a 36 amino acid peptide that is released from the endocrine cells of the distal ileum, colon, and rectum following a meal. PYY is strongly proabsorptive in the small intestine. We studied the effects of intravenous PYY on colonic water and electrolyte transport in awake dogs. Dogs had 20 cm neurovascularly intact colon Thiry-Vella fistulas (TVS) surgically constructed. Colonic transport was studied in three experimental groups. Group 1 animals received a standard mixed meal. Group 2 animals were unfed and received intravenous PYY and 100 pmol/kg/hr for two hours. This dose of PYY has previously been shown to simulate the plasma levels of PYY normally seen after a meal. Group 3 received intravenous PYY at the same dose in addition to a mixed meal. Our study shows an increase in colonic water, Na+, and Cl- absorption after a meal (P < 0.05). Infusion of PYY at a 100 pmol/kg/hr was significantly proabsorptive beginning at 60 minutes (P < 0.01). Infusion of PYY in addition to a meal further increased absorption (P < 0.05). PYY is a potent proabsorptive agent in the colon of the conscious dog. PYY, or its analogs, may be useful clinical agents in intestinal malabsorptive disorders or after bowel resection.

Topics: Animals; Colon; Dogs; Eating; Electrolytes; Female; Fistula; Gastrointestinal Hormones; Infusions, Intravenous; Intestinal Absorption; Malabsorption Syndromes; Peptide YY; Peptides; Water

The endocrine peptide YY (PYY) inhibits pancreatic secretion in animals and in man through indirect pathways. Neuropeptide Y (NPY), whose chemical structure is very close, displays similar effects. Recently, sigma ligands were shown to produce in vivo several neural pharmacologic effects that seemed indistinguishable from those of NPY. This might occur by interaction with the same (or closely related) receptors or by activation of a common final pathway. The purpose of the present work was to test whether PYY, NPY, and sigma agonists also display closely related activities on pancreatic secretion. The sigma ligands (+)-N-allyl normetazocine (d-NANM) and di(ortho-tolyl) guanidine (DTG) were used. Pancreatic secretion was stimulated by the centrally acting agent 2-deoxyglucose (2DG) in anesthetized rats. The rats were also administered either an infusion of peptide (PYY: 25-250 pmol/kg/h, NPY: 75-750 pmol/kg/h), continued for 2 h, or a bolus injection of d-NANM (3 mg/kg) or DTG (1 mg/kg). In antagonist experiments, the dopamine and sigma antagonist haloperidol (1 mg/kg, i.v.), the adrenoceptor antagonists idazoxan (0.3 mg/kg, s.c.), prazosin (0.5 mg/kg, s.c.), propranolol (1 mg/kg, s.c.) and the opiate receptor antagonist naloxone (1 mg/kg, s.c.) were injected, 5 min before the peptide infusion had begun. Neither PYY nor NPY changed basal pancreatic secretion. PYY and NPY produced a dose-related inhibition of 2DG-stimulated pancreatic secretion. The observed inhibition after 250 pmol/kg/h of PYY was volume, 78% (p < 0.01); bicarbonate, 84% (p < 0.01); protein, 78% (p < 0.01); whereas the physiologically relevant dose of 25 pmol/kg/h induced approximately 30% inhibition of these variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Fistula; Guanidines; Male; Neuropeptide Y; Pancreas; Peptide YY; Peptides; Phenazocine; Rats; Rats, Wistar