Role of Y2 receptors in the regulation of gastric tone in rats

Abstract

We set out to determine the effect of peptide YY3–36 (PYY3–36) on the gastric muscle tone in conscious rats by measuring intragastric pressure (IGP) during intragastric nutrient drink infusion. After an overnight fast, a chronically implanted gastric fistula was connected to a custom-made nutrient drink infusion system and a catheter to measure IGP. IGP was measured before and during the infusion of a nutrient drink (Nutridrink; 0.5 ml/min) until 10 ml was infused. Rats were treated with PYY3–36 (0, 33, and 100 pmol·kg−1·min−1) in combination with a subcutaneous injection of the Y2 receptor antagonists JNJ31020028 (10 mg/kg) or BIIE0246 (2 mg/kg). Experiments were also performed after subdiaphragmatic vagotomy and after pretreatment with 3 ml of nutrient drink (to mimic a fed state). IGP was compared as the average IGP during nutrient infusion, represented as means ± SE and compared using ANOVA. PYY3–36 dose dependently increased the IGP during nutrient infusion (4.7 ± 0.3, 5.7 ± 0.5 and 7.3 ± 0.7 mmHg; P < 0.01) while JNJ31020028 and BIIE0246 could block this increase [4.4 ± 0.5 ( P < 0.001) and 4.8 ± 0.4 ( P < 0.05) mmHg, respectively]. Also in vagotomized rats, PYY3–36 was able to significantly increase the IGP during, an effect attenuated by JNJ31020028. BIIE0246 and JNJ31020028 were not able to decrease the IGP when no PYY3–36 was administered. PYY3–36 increased gastric tone through an Y2 receptor-mediated mechanism that does not involve the vagus nerve. Y2 receptor antagonists were not able to decrease gastric tone without exogenous administration of PYY3–36, indicating that Y2 receptors do not play a crucial role in the determination of gastric tone in physiological conditions.