Endogenous cholecystokinin reduces food intake and increases Fos-like immunoreactivity in the dorsal vagal complex but not in the myenteric plexus by CCK1 receptor in the adult rat.

We hypothesized that endogenous CCK reduces food intake by activating the dorsal vagal complex (DVC) and the myenteric neurons of the gut. To test this hypothesis, adult rats were given camostat mesilate; a nonnutrient releaser of endogenous CCK, by orogastric gavage, and Fos-like immunoreactivity (Fos-LI) was quantified in the DVC and the myenteric plexus. The results for endogenous CCK were compared with those for exogenous CCK-8. Exogenous CCK-8 reduced food intake and stimulated Fos-LI in the DVC and in myenteric neurons of the duodenum and jejunum. In comparison, endogenous CCK reduced food intake and increased DVC Fos-LI but did not increase Fos-LI in the myenteric plexus. Similar to CCK-8, devazepide, a specific CCK(1) receptor antagonist, and not L365,260, a specific CCK(2) receptor antagonist, attenuated the reduction of food intake by camostat. In addition, Fos-LI in the DVC in response to both exogenous CCK-8 and camostat administration was significantly attenuated by vagotomy, as well as by blocking CCK(1) receptors. These results demonstrate for the first time that reduction of food intake in adult rats by endogenous CCK released by a nonnutrient mechanism requires CCK(1) receptors, the vagus nerve, and activation of the DVC, but not the myenteric plexus.

Chemical sympathectomy attenuates myenteric but not dorsal vagal complex Fos-like immunoreactivity induced by cholecystokinin-8 in the rat.

Vagotomy and capsaicin treatment attenuate dorsal vagal complex (DVC) but not myenteric Fos-like immunoreactivity (Fos-LI) induced by cholecystokinin-8 (CCK-8). The goal of this experiment is to test the role of the sympathetic nervous system in the pathway by which CCK-8 increases myenteric Fos-LI. Adult male Sprague-Dawley rats were pretreated with guanethidine sulfate (40 mg/kg daily for 5 weeks) or vehicle intraperitoneally (IP), and injected with CCK-8 (40 microg/kg) or saline IP. Fos-LI was then quantified in the DVC and the myenteric neurons of the duodenum and jejunum using a diaminobenzidine reaction. Guanethidine pretreatment attenuated myenteric but not DVC Fos-LI induced by CCK-8. These findings demonstrate that sympathetic neurons play a role in mediating the myenteric Fos-LI response to CCK. They also suggest differential mediation of myenteric and DVC responses to CCK.

Strain differences in myenteric neuron number and CCK1 receptor mRNA expression may account for differences in CCK induced c-Fos activation.

We utilized a diaminobenzidine reaction enhanced with nickel to compare dorsal vagal complex (DVC) and myenteric neuronal Fos-Like immunoreactivity (Fos-LI), in response to sulfated cholecystokinin-8 (CCK-8) (5, 10, 20, 40 microg/kg), among Sprague-Dawley (SD), Standard Long-Evans (SLE), Otsuka Long-Evans Tokushima Fatty (OLETF), and Long-Evans Tokushima Otsuka (LETO) rats. All rat strains but OLETF expressed Fos-LI in response to CCK-8. In addition, SD rats expressed more Fos-LI in the area postrema and myenteric neurons than SLE and LETO rats. To investigate the basis for these differences, we utilized cuprolinic blue staining, which stains neuronal cell bodies, to quantify the number of myenteric neurons, and a reverse transcriptase chain polymerase reaction to measure the gene expression of CCK(1) receptor in the gut. We found that SD rats have significantly more duodenal myenteric neurons than the other strains. In addition, this strain expressed significantly higher levels of the CCK(1) gene in both the duodenum and jejunum than the other strains. In conclusion, SD rats may express more myenteric Fos-LI in response to CCK due to increased numbers of myenteric neurons or more intestinal CCK(1) receptors than the other strains of rats.