第10回神経科学学術集会(大阪)1986.12.5-6

「内因性食欲調節物質の血中濃度の測定」

根本清次、藤田一郎、西野仁雄、大村裕
生理学研究所 高次液性調節

Wisterラットの静脈血より内因性摂食抑制物質である3、4-dihydroxy-butanoic acid lactone(2-DTA)と内因性摂食促進物質である2、4、5-trihydroxy pentanoic acid lactone(3-DPA)を抽出し、高感度ガスクロマトグラフィーを用いて、60時間絶食における血中濃度の変化を測定した。2-DTAは絶食前に110μMを示し、絶食後48時問で最高の150μMを示した。一方3-DPAは絶食前の230μMに対し、絶食後12時問および60時問にピークを示し、それぞれ350μM、330μMであった。さらに2-DTAの類似物質であり、静脈内および経口投与によっても強力な摂食抑制作用を有する2-buten-4-olideが血中に存在することを確認し、併せて血中濃度の測定を試みた。




Plasma concentration of endogeneous feeding modulatory substances in rats.

Neurosci. Res. Suppl. 4: s36.

Nemoto, S., Fujita, I., Nishino, H. and Oomura, Y.
National Institute for Physiological Sciences, Okazaki 444, Japan

The gamma-lactone derivatives of short chain organic acids, 3,4-dihydroxy butanoic acid lactone (2-DTA lactone), 2-buten-4-olide and 2,4,5-trihydroxy pentanoic acid lactone (3-DPA lactone) modulate feeding behavior in rats; 2-DTA lactone and 2-buten-4-olide suppress food intake, while 3-DPA lactone facilitates it (Shimizu et al. 1984; Plato-Salaman et a1. 1986). Those chemicals have been suggested as candidates of endogenous feeding modulatory substance. In the present study, we measured plasma concentration of these substances under normal and food-deprived conditions using high resolution gas chromatography. Male Wister rats (body weight 350-400g) were devided into two groups; i) normal feeding group with ad libitum food intake (N = 6) and ii) food-deprived group in which food deprivation started from 6:00 (N = 10). Half of the latter was used for measurement of 2-DTA lactone .and 3-DPA lactone, while the other half was used to measure 2-buten-4-olide. A heparinized catheter was chronically implanted into the jugular vein of rats under pentobarbital anesthesia. After one week of recovery, blood of 300 μl was collected at 9:00 and 21:00 for 3 days, then plasma was separated by centrifugation. In the normal feeding group, the plasma concentrations of 2-DTA lactone and 3-DPA lactone were 115 ± 11 μM and 230 ± 30 μM, respectively (mean ± S.D.). In the food-deprived group, a significant increase in concentration of 2-DTA lactone was found after 48-hr food deprivation (154 ± 15 μM, p < 0.05, Mann-Whitney _U-test). The concentration of 3-DPA lactone increased 12 hrs after beginning deprivation (354 ± 52 μM, p < 0.01) then returned to the original level. It increased again at 48 hrs (293 ± 52 μM, p < 0.05) and increased further at 60 hrs (330 ± 41 μM, p < 0.01) Preliminary analyses showed that the concentration of 2-buten-4-olide under normal condition was about 3 μM and increased more than three times at 48 hrs and 60 hrs after food deprivation. Timecourse of changes in the concentration of 2-buten-4-olide was similar to that of 2-DTA lactone. The present study demonstrated that 1) 2-DTA lactone, 3-DPA lactone, and 2-buten-4-olide existed in blood under normal condition, and 2) their concentration changed when rats were food deprived. The results provide further evidence for their roles as endogenous feeding modulatory substances.