Introduction
The vagus nerve plays a pivotal role in promoting meal termination and satiety by transmitting post-ingestive signals from the gastrointestinal tract. These signals are elicited by e.g. gastric distension and/or the presence of specific nutrients in the stomach. Previous research has demonstrated that the gut hormone cholecystokinin (CCK) is a potent satiety factor (Gibbs et al., 1973), which acts by stimulating vagal input into the nucleus tractus solitarii (nTS). However, the neurochemical identity of CCK-sensitive vagal afferents has not yet been determined. The present study aimed at investigating the expression of the two cholecystokininA and B receptors (CCKA-R and CCKB-R) and the newly identified cocaine- and amphetamine-regulated transcript (CART), which encodes a satiety-inducing peptide(s) (CARTp; Kristensen et al., 1998; Lambert et al., 1998), in the nodose ganglion of the vagus nerve.
Methods
Nodose ganglia and brain stems from male Sprague-Dawley rats were investigated by in situ hybridization and immunohistochemistry. Animals were divided into experimental groups and subjected to vagotomy, 48h food deprivation, 14d partial food restriction, a high-fat diet, or served as controls.
Results
By using in situ hybridization, we found that 47.4% of all nodose ganglion neuronal profiles (NP’s) expressed CART. Further investigation of CART in the vagal afferent pathway revealed the presence of CARTp-like immunoreactivity in about half of all nodose ganglion NP’s, in the vagus nerve itself (where it was seen to be transported), as well as in the vagal input portion of the nTS. In situ hybridization for CCK receptors demonstrated the presence of CCKA-R mRNA in 32.7% of nodose ganglion NP’s, whereas only 9.1% contained CCKB-R mRNA. Double-label in situ hybridization revealed that the CCKA-R-expressing cells constituted a population separate from those expressing CCKB-R. In contrast, all CCKA-R-expressing cells were seen to contain CART. Vagotomy was seen to decrease in parallel the expression of CART and CCKA-R, but to dramatically increase the percentage of cells containing CCKB-R mRNA (to 46.5%), as well as to induce CCK expression in a subpopulation of NP’s. Food deprivation, food restriction and fat diet feeding had no effect on any of the mRNA’s studied, save a small increase in CCKB-R expression that could be seen after food deprivation.
Conclusions
The present results suggest that the satiety effect of CART-derived peptides, which has previously been explained by a hypothalamic site of action, may partly be due to release of CART peptides from vagal afferents in response to post-ingestive CCK stimulation. Furthermore, these data indicate a role for vagal afferent CCK and CCKB-R in the neuronal response to injury. See also Broberger et al. (1999).
References
Broberger C., Holmberg K., Kuhar M.J. & Hökfelt T. 1999. PNAS, 96:13506-13511.
Gibbs J., Young R.C. & Smith G.P. 1973. J. Comp. Physiol. Psychol., 84:488-495.
Kristensen P. et al., 1998. Nature, 393:72-76.
Lambert P., Couceyro P.R., McGirr K.M., Dall Vecchia S.E., Smith Y & Kuhar M.J. 1998. Synapse, 29:293-298.