Neurokinin type-1 receptor antagonist inhibits enhancement of T cell functions by substance P in normal and neuromanipulated capsaicin-treated rats.
Substance P (SP) plays a major role in the regulation of the interaction between immune and nervous systems. SP administration stimulates Con A-induced proliferation of spleen and peripheral blood lymphocytes from normal and neonatally capsaicin treated rats, which correlated with enhanced IL-2 production and expression of activation antigens such as IL-2 receptor alpha chain (CD25) and RT1B MHC class II molecule. Moreover, SP markedly increased the percentage of CD5+ and CD4+ T lymphocytes in the peripheral blood of capsaicin-treated rats. Concomitant administration of SP with the non-peptide Neurokinin-1 receptor (NK1R) antagonist SR140333 completely inhibited the SP-mediated augmentation of Con A-induced PBL proliferation and IL-2 production as well as of CD4+ CD25+ and CD4+ RT1B+ T cell numbers in normal and capsaicin-treated rats. SR 140333 also blocked the increased percentage of peripheral blood CD4+ T cells induced by SP in capsaicin-treated rats.
Santoni
G
G
Department of Pharmacological Sciences and Experimental Medicine, University of Camerino, Italy. santoni@cambio.unicam.it
Perfumi
M C
MC
Spreghini
E
E
Romagnoli
S
S
Piccoli
M
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D018956:CD5 Antigens / Q000032:analysis; D002211:Capsaicin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology*
D018956:CD5 Antigens; D007376:Interleukin-2; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D003208:Concanavalin A; C085215:SR 140333; D013373:Substance P; D002211:Capsaicin