The BB2 receptor antagonist BW2258U89 attenuates the feeding responses evoked by exogenous gastrin releasing peptide-29

Abstract

This confirmatory work is aimed to test that the hypothesis that the gastrin releasing peptide (GRP) receptor – the BB2 receptor – is necessary for reduction of meal size (MS) and prolongation of the intermeal interval (IMI) by the small and the large forms of GRP in the rat, GRP-10 and GRP-29, and to confirm the sites of action regulating such responses – the vascular bed of the celiac artery (CA, supplying stomach and upper duodenum). To pursue these aims we measured first MS and IMI length in response to GRP-10 and GRP-29 (0, 0.5 nmol/kg) infused in the CA (n=8 rats) and the cranial mesenteric artery (CMA, supplying the small and part of the large intestine, n=8 rats) in near spontaneously free feeding rats pretreated with the BB2 receptor antagonist BW2258U89 (0.1 mg/kg) in the same arteries prior to the onset of the dark cycle. We found that GRP-29, but not GRP-10, infused by the CA reduced MS and prolonged the IMI by decreasing meal latency and meal duration and the BB2 receptor antagonist BW2258U89 infused in the same artery attenuated these responses. These results suggest that the BB2 receptor is necessary for reduction of MS and prolongation of the IMI by exogenous GRP-29, and the vascular bed of the CA, stomach and upper duodenum, contains sites of action regulating these feeding responses.

Cholecystokinin-33, but not cholecystokinin-8 shows gastrointestinal site specificity in regulating feeding behaviors in male rats

“…The catheterization procedures have been described in detail in our recent work (Sayegh et al, 2015; Washington et al, 2014; Washington et al, 2016a; Washington et al, 2016b; Williams et al, 2016). All catheters (Micro-Renathane Braintree Scientific R-ITC-SP 9.5) were 9.5" in length.…”

Roux-en-Y gastric bypass augments the feeding responses evoked by gastrin-releasing peptides

“…One catheter was implanted in each rat, as described previously (13, 14, 20–22). Catheters (Micro-Renathane R-ITC-SP 9.5, Braintree Scientific, Braintree MA) were 24 cm long.…”

“…We have shown that GRP alters the previous feeding behaviors, i.e. MS, IMI and SR, (7–12) through sites supplied by the celiac artery (CA, supplies stomach and upper duodenum) (13, 14). …”

“…Such changes may also alter the feeding responses evoked by the various satiety gut peptides such as exogenous and endogenous GRP. Third, the site of action regulating reduction of MS and prolongation of the IMI by GRP in normal rats resides in the area supplies by the celiac artery (CA), i.e., stomach and upper duodenum (13, 14). However, because the RYGB surgery alters the architecture of the gastrointestinal tract, the site of action regulating these feeding responses by GRP may change.…”

“…Based on our earlier work in normal rats (13, 14), here, we tested two doses of GRP-10 and GRP-29, 0.1 and 0.5 nmol/kg, infused prior to the onset of the dark cycle in the CA and in the cranial mesenteric artery (CMA, supplies small and part of the large intestine) in near spontaneously free feeding rats. Our findings suggest that indeed RYGB alters the feeding responses evoked by exogenous GRP and the sites of action regulating them in the rat.…”