Urocortin 2 acts centrally to delay gastric emptying through sympathetic pathways while CRF and urocortin 1 inhibitory actions are vagal dependent in rats

Abstract

We characterized the influence of the selective corticotropin-releasing factor 2 (CRF(2)) receptor agonist human urocortin 2 (Ucn 2), injected intracisternally, on gastric emptying and its mechanism of action compared with intracisternal CRF or urocortin (Ucn 1) in conscious rats. The methylcellulose phenol red solution was gavaged 20 min after peptide injection, and gastric emptying was measured 20 min later. The intracisternal injection of Ucn 2 (0.1 and 1 microg) and Ucn 1 (1 microg) decreased gastric emptying to 37.8 +/- 6.9%, 23.1 +/- 8.6%, and 21.6 +/- 5.9%, respectively, compared with 58.4 +/- 3.8% after intracisternal vehicle. At lower doses, Ucn 2 (0.03 microg) and Ucn 1 (0.1 microg) had no effect. The CRF(2) antagonist astressin(2)-B (3 microg ic) antagonized intracisternal Ucn 2 (0.1 microg) and CRF (0.3 microg)-induced inhibition of gastric emptying. Vagotomy enhanced intracisternal Ucn 2 (0.1 or 1 microg)-induced inhibition of gastric emptying compared with sham-operated group, whereas it blocked intracisternal CRF (1 microg) inhibitory action (45.5 +/- 8.4% vs. 9.7 +/- 9.7%). Sympathetic blockade by bretylium prevented intracisternal and intracerebroventricular Ucn 2-induced delayed gastric emptying, whereas it did not influence intravenous Ucn 2-, intracisternal CRF-, and intracisternal Ucn 1-induced inhibition of gastric emptying. Prazosin abolished the intracisternal Ucn 2 inhibitory effect, whereas yohimbine and propranolol did not. None of the pretreatments modified basal gastric emptying. These data indicate that intracisternal Ucn 2 induced a central CRF(2)-mediated inhibition of gastric emptying involving sympathetic alpha(1)-adrenergic mechanisms independent from the vagus contrasting with the vagal-dependent inhibitory actions of CRF and Ucn 1.

Impact of intracerebroventricular obestatin on plasma acyl ghrelin, des-acyl ghrelin and nesfatin-1 levels, and on gastric emptying in rats

“…As such, h/rCRF has been used as the inhibitory control for comparison in this study. From the data obtained, it is evident that an ICV injection of h/rCRF (1 nmol) significantly delays gastric emptying of a solid nutrient meal, which is consistent with a previous report that used gastric emptying of a non-nutrient, semi-liquid meal through intracisternal administration (51). Although the half-life of h/rCRF is reportedly less than 10 min in human cerebrospinal fluid (52), the results from our current study show that the ICV h/rCRF injection (1 nmol) effectively inhibits the 2-h rate of gastric emptying of a solid nutrient meal in conscious, fasted rats.…”

Perfluorooctane sulfonate influences feeding behavior and gut motility via the hypothalamus

“…The urocortin 2 gene is abundantly expressed in the hypothalamic nuclei, including the PVN, which are involved in the regulation of feeding and gut motility. Previous studies have shown that urocortin 2 suppresses food intake and delays gastric emptying (16,18). In addition, stimulation of the CRF2 receptor with urocortin 2 induces anxiogenic responses in a wide variety of rodent anxiety models (19).…”

Estrogens downregulate urocortin 2 expression in rat uterus

“…It has been reported that Ucn2 and other members of CRF family peptides delay gastric emptying, and their expression is induced by lipopolysaccharide injection in rats (Czimmer et al 2006, Yuan et al 2012; Ucn2 inhibits the hypoxia-induced apoptosis in mesenteric arterial smooth muscle cells from spontaneously hypertensive rats (Tao et al 2006), and i.v. injection of Ucn2 increases plasma angiotensin II and noradrenaline concentrations, cardiac output, heart rate and left ventricular ejection fraction, and renin activity in healthy humans (Davis et al 2007).…”