Low-affinity CCK-A receptors are coexpressed with leptin receptors in rat nodose ganglia: implications for leptin as a regulator of short-term satiety

Abstract

The paradigm for the control of feeding behavior has changed significantly. Research has shown that leptin, in the presence of CCK, may mediate the control of short-term food intake. This interaction between CCK and leptin occurs at the vagus nerve. In the present study, we aimed to characterize the interaction between CCK and leptin in the vagal primary afferent neurons. Single neuronal discharges of vagal primary afferent neurons innervating the gastrointestinal tract were recorded from rat nodose ganglia. Three groups of nodose ganglia neurons were identified: group 1 responded to CCK-8 but not leptin; group 2 responded to leptin but not CCK-8; group 3 responded to high-dose CCK-8 and leptin. In fact, the neurons in group 3 showed CCK-8 and leptin potentiation, and they responded to gastric distention. To identify the CCK-A receptor (CCKAR) affinity states that colocalize with the leptin receptor OB-Rb, we used CCK-JMV-180, a highaffinity CCKAR agonist and low-affinity CCKAR antagonist. As expected, immunohistochemical studies showed that CCK-8 administration significantly potentiated the increase in the number of c-Fospositive neurons stimulated by leptin in vagal nodose ganglia. Administration of CCK-JMV-180 eliminated the synergistic interaction between CCK-8 and leptin. We conclude that both low-and highaffinity CCKAR are expressed in nodose ganglia. Many nodose neurons bearing low-affinity CCKAR express OB-Rb. These neurons also respond to mechanical distention. An interaction between CCKAR and OB-Rb in these neurons likely facilitates leptin mediation of short-term satiety. vagal afferents; potentiation between CCK and leptin; CCK-JMV-180

Cocaine- and amphetamine-regulated transcript is the neurotransmitter regulating the action of cholecystokinin and leptin on short-term satiety in rats

“…Vagal CCKRs exist in both low-and high-affinity states (15). High-affinity vagal CCKARs mediate postprandial pancreatic enzyme secretion (15), whereas low-affinity CCKARs are involved in regulating short-term satiety (28).…”

“…High-affinity vagal CCKARs mediate postprandial pancreatic enzyme secretion (15), whereas low-affinity CCKARs are involved in regulating short-term satiety (28). Electrophysiological recording and immunohistochemical studies have shown that predominantly low-affinity CCKARs are coexpressed with LRbs in the NG (15).…”

Targeting the gastrointestinal tract to treat type 2 diabetes

“…However, it is important to note that for these studies, the testing period was only 2 weeks following DJB, and while this demonstrates that the rapid remission of diabetes following GBP may be due in part to nutrient-and hormonal-jejunal sensing mechanisms, the long-term potential of these sensing mechanisms remains unknown. The cell-type mediating the effect of jejunal leptin following DJB has not been characterized, the nodose ganglia contains leptin receptors (Li et al 2011b) and studies suggest that leptin receptors on vagal afferents, rather than intestinal epithelial cells, play a role in the development of obesity and hyperglycaemia (de Lartigue et al 2014). Thus, it is likely that leptin is acting on vagal afferents innervating the gut to regulate glucose homeostasis.…”

Functional Compensation between Cholecystokinin-1 and -2 Receptors in Murine Paraventricular Nucleus Neurons

“…Therefore, functional compensation for molecules underlying CCK-mediated satiety controls may not be limited to the two CCK receptor subtypes, but may also include other receptor signaling molecules such as leptin (49,50). For either case, the results derived from conventional knock-out mice need careful interpretation when considering single molecule functions within a system.…”