Cs. Yuan et al., Gastric effects of cholecystokinin and its interaction with leptin on brainstem neuronal activity in neonatal rats, J PHARM EXP, 295(1), 2000, pp. 177-182
Citations number
36
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Cholecystokinin (CCK) is a major gastrointestinal neuropeptide that is secr
eted in response to food ingestion. It is involved in the feedback regulati
on of gastric emptying and also modulates food intake. Leptin, a hormone th
at regulates food intake and energy balance, is secreted from adipose tissu
e, gastric mucosa, fundic glands, and other tissues. In a previous report w
e showed that gastric effects of leptin activated the nucleus tractus solit
arius (NTS) neurons responding to gastric vagal stimulation. In this study,
using the same in vitro neonatal rat preparation, we investigated the gast
ric effects of CCK and its interaction with leptin on NTS neurons receiving
gastric vagal inputs. We observed that peripheral gastric effects of CCK (
300 nM) produced a mean activation response of 271 +/- 3.9% compared with c
ontrol level (100%) in 33 (60%) neurons tested (P < .01), and this response
was abolished by a CCK-A receptor antagonist. A concentration-dependent ef
fect of CCK (10 nM-1.0 mu M) on NTS neuronal discharge frequencies was show
n. We also observed that leptin (10 nM) applied to the stomach produced a m
ean activation response of 183 +/- 5.3% in 13 (50%) NTS units that responde
d to CCK (P < .01). Furthermore, we evaluated the combined effect of CCK an
d leptin in two groups of NTS neurons. Those NTS units that showed activati
on responses to both CCK (300 nM) and leptin (10 nM) had a subadditive effe
ct that produced a mean activation response of 338 +/- 12.9% compared with
the control level in all 10 (100%) neurons tested (P < .01). Eight (36%) of
another 22 units that were not affected by either CCK (300 nM) or leptin (
10 nM) alone had an activation response (151 +/- 5.2%; P < .05) when the sa
me concentrations of CCK and leptin were applied together. Subsequently, by
comparing the effects of CCK and leptin on a whole-stomach preparation to
a partial-stomach preparation, we examined the area of the stomach in which
gastric receptors contributed most to NTS unitary activity. We showed that
the distal stomach containing the pylorus determined CCK gastric activity,
whereas both the proximal and distal stomach are important for leptin's ef
fect. Our data suggest that leptin modulates the potency of CCK signals tha
t modify food intake in the neonatal rat.