Nitric oxide donors enhance rectal absorption of macromolecules in rabbits

被引:48
作者
Utoguchi, N [1 ]
Watanabe, Y [1 ]
Shida, T [1 ]
Matsumoto, M [1 ]
机构
[1] Showa Coll Pharmaceut Sci, Dept Pharmaceut Sci, Machida, Tokyo 1948543, Japan
关键词
rectal mucosa; absorption enhancer; nitric oxide;
D O I
10.1023/A:1011920530771
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Purpose. The objective of this investigation is to evaluate the potential of nitric oxide (NO) donors as a new class of absorption enhancers which may act on intestinal epithelial cells through epithelial actions of the chemical mediator, NO. Methods. Suppositories containing NO donors and insulin were administered into the rabbit rectum. After administration of the suppository, blood samples were collected from the auricular vein. The plasma insulin and glucose concentrations were determined. Results. The NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP, 4 mg) induced a significant increase in the rate of insulin absorption from the rectum. Administration of a suppository containing SNAP without insulin affected neither the plasma insulin nor the plasma glucose concentration. Other NO donors, NOR1 and NOR4, also induced increases in the insulin absorption. The absorption enhancement effect of SNAP was inhibited by coadministration of the NO scavenger carboxy-PTIO. SNAP also enhanced RTC-dextran (MW 4,000) absorption. Little cytotoxicity of SNAP (3.0 mg/ml) as assessed in terms of the rate of lactate dehydrogenase (LDH) release from Caco-2 cells was detected for 2 h of incubation. Conclusions, These findings suggest that NO enhanced macromolecular absorption from the rectum without mucosal cell damage, and that NO donors can act as potent absorption enhancers.
引用
收藏
页码:870 / 876
页数:7
相关论文
共 29 条
[1]   EPITHELIAL TRANSPORT OF DRUGS IN CELL-CULTURE .8. EFFECTS OF SODIUM DODECYL-SULFATE ON CELL-MEMBRANE AND TIGHT JUNCTION PERMEABILITY IN HUMAN INTESTINAL EPITHELIAL (CACO-2) CELLS [J].
ANDERBERG, EK ;
ARTURSSON, P .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1993, 82 (04) :392-398
[2]   REGULATION OF EPITHELIAL TIGHT JUNCTION PERMEABILITY BY CYCLIC-AMP [J].
DUFFEY, ME ;
HAINAU, B ;
HO, S ;
BENTZEL, CJ .
NATURE, 1981, 294 (5840) :451-453
[3]   A SEMIAUTOMATED MICROCULTURE METHOD FOR INVESTIGATING GROWTH INHIBITORY EFFECTS OF CYTO-TOXIC COMPOUNDS ON EXPONENTIALLY GROWING CARCINOMA-CELLS [J].
FINLAY, GJ ;
BAGULEY, BC ;
WILSON, WR .
ANALYTICAL BIOCHEMISTRY, 1984, 139 (02) :272-277
[4]   SPECIFIC DETERMINATION OF BLOOD GLUCOSE WITH O-TOLUIDINE [J].
HYVARINEN, A ;
NIKKILA, EA .
CLINICA CHIMICA ACTA, 1962, 7 (01) :140-&
[5]   FLUORESCENCE STUDY OF THE MEMBRANE-PERTURBING ACTION OF SODIUM CAPRYLATE AS RELATED TO PROMOTION OF DRUG ABSORPTION [J].
KAJII, H ;
HORIE, T ;
HAYASHI, M ;
AWAZU, S .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1988, 77 (05) :390-392
[6]   New reagents for controlled release of nitric oxide. Structure-stability relationships [J].
Kato, M ;
Nishino, S ;
Ohno, M ;
Fukuyama, S ;
Kita, Y ;
Hirasawa, Y ;
Nakanishi, I ;
Takasugi, H ;
Sakane, K .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1996, 6 (01) :33-38
[7]   FR144420, A NOVEL, SLOW, NITRIC OXIDE-RELEASING AGENT [J].
KITA, Y ;
OHKUBO, K ;
HIRASAWA, Y ;
KATAYAMA, Y ;
OHNO, M ;
NISHINO, S ;
KATO, M ;
YOSHIDA, K .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1995, 275 (02) :125-130
[8]   Nitric oxide (nitrogen monoxide, NO) stimulates insulin secretion by inducing calcium release from mitochondria [J].
Laffranchi, R ;
Gogvadze, V ;
Richter, C ;
Spinas, GA .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1995, 217 (02) :584-591
[9]  
LEE VHL, 1991, CRIT REV THER DRUG, V8, P90
[10]  
LINDMARK T, 1995, J PHARMACOL EXP THER, V275, P958