Involvement of tachykinin receptors in sensitisation to cow’s milk proteins in guinea pigs

Abstract

Background-There is growing evidence for a pivotal role for tachykinins in gut neuroimmune interactions. Aims-To determine whether NK1, NK2, and NK3 tachykinin receptors are involved in milk protein induced allergic sensitisation. Methods-Eight groups of 12 DunkinHartley guinea pigs (250-300 g) were used. Four groups were sensitised to milk proteins for three weeks. During this period, these animals were injected intraperitoneally each day with NK1 (SR 140333; 0.3 mg/kg), NK2 (SR 48968; 5 mg/kg), or NK3 (SR 142801; 5 mg/kg) receptor antagonist or vehicle. The fifth group had water available instead of milk and was used as a non-sensitised control. The three other groups received the NK receptor antagonists for three weeks but were not sensitised to milk proteins. Results-Sensitised animals treated with NK1 and NK3 receptor antagonists had both lower IgE and IgG serum titres, evaluated by passive cutaneous anaphylaxis, and lower specific IgG serum titres, determined by enzyme linked immunosorbent assay (ELISA), than vehicle treated animals. Sensitisation induced an increase in intestinal mast cell number which was abolished by treatment with the NK1 receptor antagonist. Antigenic challenge-induced jejunal hypersecretion was also blocked by treatment with the NK1 receptor antagonist. Conclusion-In guinea pigs, NK1 and NK3 but not NK2 receptors are involved in sensitisation to cow's milk. However, NK1 but not NK3 receptor antagonists abolish both the hypermastocytosis induced by food allergy and the hypersecretion induced by antigenic challenge, suggesting diVerent roles for NK1 and NK3 receptors in the mechanisms of sensitisation to -lactoglobulin. (Gut 1999;44:497-503)

Stress-induced barrier disruption of rat follicle-associated epithelium involves corticotropin-releasing hormone, acetylcholine, substance P, and mast cells

“…The involvement of SP in inflammation and stress has been shown previously 23,49,50 and there are direct or indirect evidences on the role of SP on gut paracellular permeability 51–53 . As mentioned, permeability to 51 Cr‐EDTA was unaffected by WAS, however, the levels in stressed animals were decreased by NK‐1R blocking, indicating a modulating role for SP in 51 Cr‐EDTA permeability.…”

Involvement of Tachykinins in Intestinal Inflammation

“…The observation that recombinant NEP and administration of the NK 1 receptor antagonist SR 140333 restored baseline conditions [17] is further evidence that SP is involved in intestinal inflammation and hypersecretion. Jejunal hypersecretion induced by antigenic challenge was likewise inhibited by SR 140333 administration, but not by NK 2 or NK 3 receptor antagonists [95].…”

Neurokinin NK1 and NK3 receptors as targets for drugs to treat gastrointestinal motility disorders and pain

“…NK 3 receptor antagonism may also reduce certain effects of immune (IgE and IgG serum litres reduced after sensitisation to cow's milk, but the increase in intestinal mast cell numbers was reduced only by NK 1 receptor antagonism; Gay et al , 1999 ) and inflammatory (TNBS‐induced neurogenic colitis reduced by NK 3 or NK 2 receptor antagonism in guinea‐pigs; Mazelin et al , 1998 ) stimuli on gut function. The mechanisms of these actions are unclear, but as for the above studies on intestinal motility and sensation, the data are consistent with an activity‐dependent role for the receptor.…”