The tripeptide feG ameliorates systemic inflammatory responses to rat intestinal anaphylaxis

Abstract

Background: Food allergies are generally associated with gastrointestinal upset, but in many patients systemic reactions occur. However, the systemic effects of food allergies are poorly understood in experimental animals, which also offer the opportunity to explore the actions of anti-allergic drugs. The tripeptide D-phenylalanine-D-glutamate-Glycine (feG), which potentially alleviates the symptoms of systemic anaphylactic reactions, was tested to determine if it also reduced systemic inflammatory responses provoked by a gastric allergic reaction.

Salivary gland derived peptides as a new class of anti-inflammatory agents: review of preclinical pharmacology of C-terminal peptides of SMR1 protein

“…Oral challenge in OA sensitized rats induces systemic effects including increased circulating leukocytes, leukocyte infiltration into the heart, increased vascular permeability, and pulmonary inflammation [ 42 ]. Changes in vascular permeability occurred within 30 minutes, peripheral blood neutrophilia appeared by 3 hours, and significant accumulation of neutrophils in the heart, detected by a 75% increase in myeloperoxidase (MPO) content, was seen at 24 hours after oral OA challenge.…”

“…In peritoneal neutrophils collected from OA sensitized rats 24 hours after challenge, pre-treatment with feG had no effect on expression of the alpha integrin CD 11b but down regulated expression of the beta 1 integrin CD49 d (Alpha-4 integrin chain) [ 42 ]. In vitro incubation of human neutrophils with feG inhibited PAF induced neutrophil migration (see Figure 12 ) as well as expression of CD 11b [ 39 ].…”

A New Conformationally Restricted Mimetic of Dipeptide EG – Synthesis of an Analogue of FEG

“…In fact, FEG was reported to display anti-hypotensive properties against anaphylactic shock, [5] together with a potent inhibition of intestinal anaphylaxis and inhibitory effects on inflammatory reactions. [9] On the other hand, feG has anti-inflammatory [ properties in allergic airways inflammation in BrownNorway rats, [10] reduces endotoxin-provoked perturbation of intestinal motility and inflammation [11,12] and regulates leukocyte adhesion to the heart. [13,14] Thus, at first we devised that compound 2, having a (3R,4S) configuration, which was recently synthesized in our laboratory, [15] could be an attractive starting material for the preparation of a conformationally restricted dipeptide EG (Glu-Gly) suitable for the insertion in FEG, in order to change or improve its biological activity.…”