Regulation of leptin distribution between plasma and cerebrospinal fluid by cholecystokinin receptors

Abstract

Cholecystokinin (CCK) is a postprandial hormone that elicits a satiating effect and regulates feeding behaviour. CCK has been shown to enhance the effect of leptin in several experimental paradigms. The goal of this work was to characterize the effect of endogenous CCK on plasma leptin content by using CCK receptor antagonists. Therefore, we administered SR-27897, a selective CCK1 receptor antagonist, and L-365260, a selective CCK2 receptor antagonist, to fed and food-deprived rats and determined plasma leptin concentration by enzyme immunoassay. Plasma insulin and glucose concentration as well as food intake were also determined. Under our conditions, SR-27897 increased plasma concentration of leptin both in fed and food-deprived rats. It also increased food intake as well as plasma concentration of insulin in fed animals. L-365260 increased plasma leptin concentration only in fed rats. In animals receiving exogenous leptin, CCK-8 increased the ratio between the concentration of leptin in cerebrospinal fluid and plasma. These results show that CCK receptor antagonists increases plasma concentration of leptin and suggest that endogenous CCK may facilitate the uptake of plasma leptin to the cerebrospinal fluid.

Figure 1

(a) Effect of SR-27,897 (0.3 mg kg⁻¹) on insulin plasmatic concentration. Vehicle (open columns) or SR-27,897 (hatched columns) were administered 120 min before the lights were off. Values are means±s.e.m. of 8 – 10 animals. (b) Effect of L-365,260 (1 mg kg⁻¹) on insulin plasma concentration. Values are means± s.e.m. of 8 – 10 animals.

Figure 2

(a) Effect of SR-27,897 (0.3 mg kg⁻¹) on leptin plasmatic concentration. Vehicle (open columns) or SR-27,897 (hatched columns) were administered 120 min before the lights were off. Values are means±s.e.m. of 8 – 10 animals. **P<0.01, compared to the control group (Newman – Keuls' test). (b) Effect of L-365,260 (1 mg kg⁻¹) on leptin plasma concentration. Values are means± s.e.m. of 8 – 10 animals. *P<0.05, compared to the control group (Newman – Keuls' test).

Figure 3

Effect of SR-27,897 (0.3 mg kg⁻¹) and L-365,260 (1 mg kg⁻¹) on food intake. Values are means±s.e.m. of 8 – 10 animals. *P<0.05, compared to the control group (Newman – Keuls' test).

Figure 4

Effect of CCK-8 on the ratio between CSF and plasma leptin concentration. Values are means±s.e.m. of five to six animals. *P<0.05 (Newman – Keuls' test).