Several Receptors Mediate the Antisecretory Effect of Peptide YY, Neuropeptide Y, and Pancreatic Polypeptide on VIP-Induced Fluid Secretion in the Rat Jejunum In Vivo

doi:10.1016/S0196-9781(97)00069-7

Peptides

Volume 18, Issue 4, 1997, Pages 551-557

https://doi.org/10.1016/S0196-9781(97)00069-7 Get rights and content

Abstract

Souli, A., J. Chariot, T. Voisin, O. Presset, A. Tsocas, A. Balasubramaniam, M. Laburthe and C. RozÉ. Several receptors mediate the antisecretory effect of peptide YY, neuropeptide Y, and pancreatic polypeptide on VIP-induced fluid secretion in rat jejunum in vivo. Peptides 18(4) 551–557, 1997.—Several Y receptor subtypes have been cloned and/or pharmacologically characterized that mediate the effects of the regulatory peptides peptide YY (PYY), neuropeptide Y (NPY), and pancreatic polypeptide (PP). These peptides possess antisecretory properties on the intestine. This effect can be blocked in vivo by neural antagonists, suggesting the intervention of neural receptors, although epithelial PYY-preferring receptors have been evidenced on jejunal crypt cells. The purpose of the present experiments was to compare the antisecretory properties in vivo of a series of PYY and NPY derivatives with various affinities for different Y receptor subtypes, in order to determine which subtypes were involved. A model of VIP-stimulated secretion by rat jejunal loops was used. The results were compared with the binding affinities for PYY-preferring receptors determined on rat jejunal crypt cell membranes. Full-length PYY(1–36) was about three times more potent than NPY(1–36), and 10 times more potent than PP in the low dose range. PP, however, had a low efficacy limited to about 50% inhibition of VIP effect. Both Y₁ agonists ([Leu³¹,Pro³⁴]PYY and [Leu³¹,Pro³⁴]NPY), and Y₂ agonists [C-terminal fragments ranging from PYY(3–36) and NPY(3–36) to PYY(22–36) to NPY(22–36)] displayed potent antisecretory properties. PYY derivatives and fragments were always more potent than their respective NPY counterparts. In contrast, Y₁ derivatives and PP had very low affinity for the epithelial PYY receptor as measured in vitro by radioreceptor assay. These data suggest that the antisecretory effect of PYY/NPY/PP peptides in vivo involves the effets of several receptors: a Y₂-like, PYY-preferring receptor identical to the epithelial receptor, a Y₁-like receptor, and a third receptor with high affinity for PP.

Section snippets

Animals

Male Wistar rats weighing 180–200 g (Iffa-Credo, Les Oncins, F 69210 L'Arbresle) were fasted for 24 h with free access to water before the experiments.

Peptides

PYY(1–36) (pig, rat), NPY(1–36) (human, rat), PP (human), PYY(3–36), PYY(13–36), NPY(3–36), NPY (13–36), NPY(22–36), [Leu³¹,Pro³⁴]PYY, [Leu³¹,Pro³⁴] NPY, and VIP (human, pig, rat) were purchased from Neosystem, Strasbourg France. PYY(22–36) and N-α-AcPYY(22–36) were generous gifts of A. Balasubramaniam (University of Cincinnati Medical Center,

Effect of PYY, NPY, and PP on VIP-Stimulated Fluid Jejunal Secretion

PYY(1–36) inhibited in a dose-related manner VIP-stimulated jejunal fluid secretion. In preliminary experiments, two different doses of VIP were used. In basal conditions, the mean water net flux was −46.9 ± 3.4 μl/cm/30 min, indicating a basal absorption. After stimulation by 100 μg/kg/h of VIP, the jejunal secretion reached 39 ± 2.7 μl/cm/30 min; the inhibition was complete after 300 pmol/kg of PYY and the ID₅₀ was 30 pmol/kg of PYY (not shown). After stimulation by 30 μg/kg/h of VIP, the

Discussion

The present study was designed to investigate the subtypes of Y receptors involved in the jejunal antisecretory effect of PYY and NPY by comparing the effects of the full-length peptides with different fragments or analogues on VIP-stimulated jejunal secretion in the rat in vivo.

The model chosen for the present work was the jejunal ligated loop in situ in anesthetized rats. In a previous article ([43]), we showed that this model was appropriate to evidence the antisecretory effect of PYY and

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Several Receptors Mediate the Antisecretory Effect of Peptide YY, Neuropeptide Y, and Pancreatic Polypeptide on VIP-Induced Fluid Secretion in the Rat Jejunum In Vivo

Abstract

Section snippets

Animals

Peptides

Effect of PYY, NPY, and PP on VIP-Stimulated Fluid Jejunal Secretion

Discussion

Peptides

J. Biol. Chem.

Biochim. Biophys. Acta

Regul. Pept.

Peptides

Peptides

Life Sci.

J. Biol. Chem.

FEBS Lett.

Gastroenterology

Peptides

J. Biol. Chem.

J. Biol. Chem

Peptides

Anal. Biochem.

Eur. J. Pharmacol.

Lancet

J. Biol. Chem.

Eur. J. Pharmacol.

Peptides

J. Biol. Chem.

J. Biol. Chem.

Life Sci.

Life Sci.

J. Biol. Chem.

Inhibition of VIP-stimulated ion transport by a novel Y-receptor phenotype in rabbit distal colon

Am. J. Physiol.

Structure-activity relationships of neuropeptide Y analogues with respect to Y1 and Y2 receptors

Biopolymers (Pept. Sci.)