Central CRF inhibits gastric emptying of a nutrient solid meal in rats: the role of CRF₂receptors

Abstract

Corticotropin-releasing factor (CRF)-related peptides exhibit different affinity for the receptor subtypes 1 and 2 cloned in the rat brain. We investigated, in conscious rats, the effects of intracisternal (IC) injection of CRF (rat/human) on the 5-h rate of gastric emptying of a solid nutrient meal (Purina chow and water ad libitum for 3 h) and the CRF receptor subtype involved. CRF, urotensin I (suckerfish), and sauvagine (frog) injected IC inhibited gastric emptying in a dose-dependent manner, with ED50 values of 0.31, 0.13, and 0.08 μg/rat, respectively. Rat CRF-(6—33) (0.1–10 μg ic) had no effect. The nonselective CRF1and CRF2 receptor antagonist, astressin, injected IC completely blocked the inhibitory effect of IC CRF, urotensin I, and sauvagine with antagonist-to-agonist ratios of 3:1, 10:1, and 16:1, respectively. The CRF1-selective receptor antagonist NBI-27914 injected IC at a ratio of 170:1 had no effect. These data show that central CRF and CRF-related peptides are potent inhibitors of gastric emptying of a solid meal with a rank order of potency characteristic of the CRF2receptor subtype affinity (sauvagine > urotensin I > CRF). In addition, the reversal by astressin but not by the CRF1-selective receptor antagonist further supports the view that the CRF2 receptor subtype is primarily involved in central CRF-induced delayed gastric emptying.

Remodeling of networks of interstitial cells of Cajal in a murine model of diabetic gastroparesis.

“…Currently, the most commonly used parameter to quantify gastric emptying is its half-time, and this factor is determined by scintigraphic analysis (36). This technique has not yet been applied to mice, and therefore we used a previously described technique for testing gastric emptying in this species (21,22). This technique is based on measuring the contents of the stomach remaining at intervals after a test meal and expressing this weight as a percentage of the total weight of the meal.…”

“…Gastric emptying was measured by a method modified from a previously described technique (21,22): After an overnight fast with free access to water, a 0.25 ml meal, consisting of one part powdered mouse diet suspended in two parts of water (wt/wt), was given by gavage using an 18-gauge animal feeding tube (Fisher Scientific, Pittsburgh, PA) under brief CO 2 anesthesia. After the meal, mice were returned to their home cages without food or water and killed after 3 h. The stomachs were removed after clamping the esophagus at the cardia and the pylorus.…”

Human urocortin II, a new CRF-related peptide, displays selective CRF2-mediated action on gastric transit in rats

“…After bead insertion, conscious rats were placed in individual plastic cages without water or food. The time required for expulsion of the bead (in min) was monitored over 4 h. Gastric emptying of the ingested meal was assessed 4 h after food removal as previously described (20). Animals were euthanized by CO 2 inhalation, the abdominal cavity was rapidly opened, the pylorus and cardia were clamped, and the stomach was removed and its contents weighed.…”

Expression of corticotropin releasing factor (CRF) in the enteric nervous system of the jejunum of sheep

“…Moreover, it has been documented that CRF may aff ect gut function. Central administration of CRF evoked inhibition of gastric motility, emptying, and acid secretion as well as stimulation of colonic propulsion and these effects were mediated through both CRF1 and CRF2 receptors (Druge et al, 1989;Martinez et al, 1998;Martinez and Tache, 2001). Additionally, CRF when administrated peripherally also inhibited gastric emptying (Martinez et al, 1999) as well as increasing duodenal (Mayer et al, 1992), ileal (la Fleur et al, 2005) and colonic motility (Tsukamoto et al, 2006).…”