Basic—Alimentary TractCocaine- and Amphetamine-Regulated Transcript Mediates the Actions of Cholecystokinin on Rat Vagal Afferent Neurons
Section snippets
Materials
CCK8s and ghrelin were obtained from Bachem (St. Helens, Merseyside, UK); leptin and phorbol 12-acetate-13-myristate ester (PMA) were obtained from Sigma (Poole, Dorset, UK). CARTp (55–102, human) was obtained from American Peptide Company (Sunnyvale, CA). Brefeldin-A (BFA) was obtained from Epicentre Biotechnologies (Madison, WI).
Animals
Adult male Wistar rats (225–300 g) were housed at 22°C under a 12-hour light/dark cycle with ad libitum access to food and water, unless stated otherwise. Studies
CCK Releases CARTp From Nodose Ganglion Neurons
To determine whether CARTp is secreted from vagal afferent neurons in response to stimulation, we cultured neurons for 72 hours and then transferred cells into serum-free medium overnight before treatment with CCK8s for 2 hours. The concentration of CARTp in media from unstimulated cells was 113 ± 20 pg/mL and in response to CCK8s was increased approximately 3-fold (P < .001). Leptin augmented the action of CCK8s and ghrelin inhibited it (P < .001 in both cases), but neither had any action
Discussion
Vagal afferent neurons serving the gut mediate the effects of a variety of peripheral signals on food intake and gastric emptying. One of the best studied hormones stimulating these neurons is CCK, and previous studies have shown that this is associated with inhibition of gastric emptying,5, 6 inhibition of food intake,8, 34 stimulation of pancreatic secretion,35 and inhibition of gastrointestinal inflammatory responses.36 We have reported that CCK stimulates expression in vagal afferent
Acknowledgments
We are grateful to Drs M. Kuhar and D. Ginty for the gift of plasmids.
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by grants from the Biotechnology and Biological Sciences Research Council and MRC (GJD), and National Institutes of Health (HER, NIHDK41004).