Cholecystokinin and bombesin activate neuronatin neurons in the nucleus of the solitary tract.

Neuronatin (Nnat) is involved in the regulation of cellular molecular signaling and appears to be also linked to metabolic processes. The gastrointestinal peptides cholecystokinin (CCK) and bombesin (BN) have an effect on the short-term inhibition of food intake and induce neuronal activation in different brain nuclei, prominently in the nucleus of the solitary tract (NTS) involved in the modulation of food intake. The aim of the study was to examine if Nnat immunoreactivity is detectable in the NTS, and whether peripheral CCK-8S or BN cause c-Fos activation of Nnat neurons. Non-fasted male Sprague-Dawley rats received an intraperitoneal (i.p.) injection of 5.2 or 8.7 nmol CCK-8S/kg or 26 or 32 nmol BN/kg (n = 4 all groups) or vehicle solution (0.15 M NaCl; n = 7). The number of c-Fos neurons was determined 90 min post injection in the NTS and dorsal motor nucleus of the vagus (DMV). We observed Nnat immunoreactive neurons in the NTS and DMV. CCK-8S (25-fold and 51-fold, p = 0.025 and p = 0.001) and BN (31-fold and 59-fold, p = 0.007 and p = 0.001) at both doses increased the number of c-Fos positive neurons in the NTS. CCK and BN did not show a significant effect in the DMV. Both doses of CCK-8S (24-fold and 48-fold p = 0.011 and p = 0.001) and bombesin (31-fold and 56-fold, p = 0.002 and p = 0.001) increased the number of activated Nnat neurons in the NTS (p = 0.001) compared to the vehicle group, while in the DMV no significant increase of c-Fos activation was detected. In conclusion, i.p. injected CCK-8S or BN induce an increased neuronal activity in NTS Nnat neurons, giving rise that Nnat may play a role in the regulation of food intake mediated by peripheral CCK-8S or BN.