跳至主要内容

Sodium caprate enables the blood pressure-lowering effect of Ile-Pro-Pro and Leu-Lys-Pro in spontaneously hypertensive rats by indirectly overcoming PepT1 inhibition

Author：John P.Gleeson, Jesús M.Frías, Sinéad M.Ryan, David J.Brayden   《European Journal of Pharmaceutics and Biopharmaceutics》

ABSTRACTS
The tripeptides, Ile-Pro-Pro (IPP) and Leu-Lys-Pro (LKP), inhibit angiotensin-converting enzyme (ACE) resulting in lowered blood pressure. Our hypothesis was that the medium chain fatty acid permeation enhancer, sodium caprate (C10), may prevent the decrease in permeability of the tripeptides when PepT1 is inhibited by glycyl-sarcosine (Gly-Sar), a situation that may occur in the presence of food hydrolysates. Using Caco-2 monolayers and isolated rat jejunal tissue, the apparent permeability coefficients (Papp) of [3H]-IPP and [3H]-LKP were assessed in the presence of Gly-Sar with and without C10. Gly-Sar decreased the Papp of both tripeptides across monolayers and isolated jejunal tissue, but C10 restored it. C10likely increased the paracellular permeability of the tripeptides, as indicated by immunofluorescence changes in tight junction proteins in Caco-2 monolayers accompanied by a concentration-dependent decrease in transepithelial electrical resistance (TEER). [3H]-IPP and [3H]-LKP were orally-gavaged to normal rats with Gly-Sar, C10, or with a mixture. Plasma levels of both peptides were reduced by Gly-Sar to less than half that of the levels detected in its absence, but were restored when C10 was co-administered. In spontaneously hypertensive rats (SHRs), unlabelled IPP and LKP lowered blood pressure when delivered either by i.v. or oral routes. Oral gavage of Gly-Sar reduced the hypotensive action of peptides in SHRs, but the effect was restored in the presence of C10. In conclusion, there was a reduction in the hypotensive effects of IPP and LKP in SHRs when intestinal PepT1 was inhibited by Gly-Sar, but C10 may circumvent this by enhancing paracellular permeability.

Graphical abstract


KEY WORDS
Intestinal peptide transport; PepT1; Nutraceuticals; Antihypertensive agents; Intestinal permeation enhancers; Sodium caprate
SCREENSHOT

RELATED PRODUCTS
IPP (PubChem CID: 9949212) and LKP (PubChem CID: 24978508) were obtained from China Peptides (China)
CHAINING
https://www.sciencedirect.com/science/article/abs/pii/S0939641117308986


标签：

评论

发表评论

此博客中的热门博文

Deubiquitinating enzyme USP9X regulates cellular clock function by modulating the ubiquitination and degradation of a core circadian protein BMAL1

Author：Yang Zhang, Chunyan Duan, Jing Yang, Suping Chen,  Qing Liu, Liang Zhou, Zhengyun Huang, Ying Xu, Guoqiang Xu     《Biochemical Journal》 ABSTRACTS Living organisms on the earth maintain a roughly 24 h circadian rhythm, which is regulated by circadian clock genes as well as their protein products. Post-translational modifications of core clock proteins could affect the circadian behavior. Although ubiquitination of core clock proteins was studied extensively, the reverse process, deubiquitination, has only begun to unfold and the role of this regulation on circadian function is not completely understood. Here, we use affinity purification and mass spectrometry analysis to identify probable ubiquitin carboxyl-terminal hydrolase FAF-X (USP9X) as an interacting protein of the core clock protein aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL or BMAL1). Through biochemical experiments, we discover that USP9X reduces BMAL1 ubiquitina...
发表评论
阅读全文

CAS:85466-18-8|Thymopoietin II (32-35)|RKDV

Contact： Liven Qian(钱叶华)-Custom Peptide Mobile: 13761298676（微信） Email：cps037@chinapeptides.net QQ：2880526724 ChinaPeptides Co., Ltd./强耀生物科技有限公司 Name Thymopoietin II (32-35) Code [85466-18-8] The alias Thymopoietin II (32-35) Sequence (single letter abbreviation) RKDV Sequence (three-letter abbreviation) H-Arg-Lys-Asp-Val-OH (trifluoroacetate salt) A basic description TP-4 and TP-3; shortest active thymopoietin II fragments described that exhibit potent immunoregulatory properties in vitro and in vivo. solubility The molecular weight 516.6 Chemical formula C21H40N8O7 The purity 80%，90%，95%，98%，99% Weight 1mg,5mg,10mg,50mg,100mg,1g Storage conditions Store at -20°C. Keep tightly closed. Store in a cool dry place. Number of Residues: 4 1-Letter Code: RKDV 3-Letter Code: Arg-Lys-Asp-Val Molecular weight (Mr): 516.6 g/mol Isoelectric point: 10.1 Net charge at pH 7.0: 1.0 Average hydrophilicity: 1.9 Ratio of hydrophilic residues / total number of residues...
1 条评论
阅读全文

Targeting the leptin receptor: To evaluate therapeutic efficacy and anti-tumor effects of Doxil, in vitro and in vivo in mice bearing C26 colon carcinoma tumor

Author：Shahrzad Amiri Darban, Sara Nikoofal-Sahlabadi,  Nafise Amiri, Nafiseh Kiamanesh, Amin Mehrabian, Bamdad Zendehbad, Zahra Gholizadeh, Mahmoud Reza Jaafari     《Colloids and Surfaces B: Biointerfaces》 ABSTRACTS Leptin is an appetite regulatory hormone that is secreted into the blood circulation by the adipose tissue and it functions via its over expressed receptors (Ob-R) in a wide variety of cancers. In the present study, the function of a leptin-derived peptide (LP16, 91–110 of Leptin) was investigated as a targeting ligand to decorate PEGylated liposomal doxorubicin (PLD, Doxil ? ) surface and the anti-tumor activity and therapeutic efficacy of Doxil in C26 (Colon Carcinoma) tumor model were also evaluated. As a result of this, Doxil with different LP16 peptide density (25, 50, 100 and 200 peptide on the surface of each liposome) was successfully prepared and characterized. In vitro results showed significant enhanced cytotoxicity and cellular b...
发表评论
阅读全文