Factors affecting the intestinal absorption of orally-administered physiologically active proteins in rat
| Project/Area Number |
08456065
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
食品科学・栄養科学
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| Research Institution | Nagoya University |
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Principal Investigator |
KAKINUMA Atsushi Nagoya U.Applied Biological Sciences Prof., 農学部, 教授 (50252276)
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| Co-Investigator(Kenkyū-buntansha) |
ODA Hiroaki Nagoya U.Applied Biological Sciences Assoc.Prof., 農学部, 助教授 (20204208)
HORIO Fumihiko Nagoya U.Applied Biological Sciences Assoc.Prof., 農学部, 助教授 (20165591)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥5,200,000 (Direct Cost: ¥5,200,000)
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| Keywords | Intestinal absorption of proteins / Intestinal absorption of proteases / Orally-available anti-inflammatory protease / Serratia protease / Development of orally-available high mole-cular weight pharmacenticals / lncrease of intestinal absorption of proteins by lipids / surfactin / lymph vessel / lymph |
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| Research Abstract |
Our observation that Serratia protease (SP,MW 50,600) orally-administered to scalded rats dramatically repressed the enhancement of fibrinolysis and blood vessel permeability both induced by the scalding, strongly suggested its intestinal absorption. To investigate this possibility, we established a highly-sensitive EIA and a protease assay for determining SP concentration in rat plasma, and succeeded in demonstrating that a portion of orally-administered SP was absorbed from the intestinal tract in an enzymatically active form. This was the first observation clearly indicating that orally-administered physiologically active proteins can be transferred from the intestine to the blood stream without losing its original activity to exert eventually a systemic function in the body.
Since, we have been trying to identify any physiological or nutritional factors that may control the degree of the intestinal absorption of SP in rat. In the preious experiment, we investigated the effect of age
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and feeding on the absorption (A.Kakinuma : in Abstracts of Research Project, Grant-in-Aid for Scientific Research (B) (1995, Project No.06454083).
Results of the present investigation are summarized as follows.
1.We analyzed the time-course of the change of SP concentration in portal vein plasma, tail vein plasma and in mesenteric lymph after oral administration to know that SP is first absorbed from intestine by way of lymph and then transferred to blood.
2.The coexistence of such substances as proteins and lipids in orally-administered SP solutions influenced the degree and the pattern of SP absorption. Especially, the presence of 60% (v/v) corn oil increased the amount of SP absorbed more than 10 times by incorporating SP into the emulsion formed by oil and water and enabling SP to escape from the denaturation by gastric acid and subsequent degradation by proteinases.
3.Surfactin, an anionic peptidelipid surfactant produced by B.subtilis and isolated by us (Biochem.Biophys.Res.Commun.31,488 (1968)) gave an effect different from that of corn oil described in 2. Although SP administered together with surfactin was completely inactivated in stomach (pH3), some SP-derived molecule, presunably inactivated SP,was absorbed, transferred to blood and detected in plasma by our EIA.Its maximum plasma concentration, increased 1.4-1.5 times, was realized at 1h after administration, in contrast to 2h after adminstration in the absence of surfactin. Surfactin seems to influence the molecular mechanism of absorption of SP in addition to the stability of SP in stomach and intestine. Less
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Report
(3 results)
Research Products
(1 results)
