Enhancement of mitogen-induced lymphocyte proliferation by some inhibitors of alkaline phosphatase and diamine oxidase.
We selected various compounds [bromolevamisole, levamisole, cimetidine, L-homoarginine, 2,3,5,6-tetrahydroimidazo-(2,1-b)thiazole (IT), imidazole, theophylline] previously reported as inhibitors of alkaline phosphatase (ALP) and/or diamine oxidase (DAO) and studied their activity on concanavalin A (ConA)-induced mouse spleen cell lymphocyte proliferation. According to the Ki values, the decreasing order of potency for ALP inhibition was: bromolevamisole, levamisole, theophylline, cimetidine, IT, imidazole and L-homoarginine. The order of potency was different for DAO inhibition. Cimetidine was the most potent inhibitor of DAO, followed by bromolevamisole, levamisole, IT, imidazole and L-homoarginine. Theophylline had no inhibitory effect on DAO. We show that these compounds, except theophylline, enhance ConA-induced lymphocyte proliferation. Similarly, all the compounds except imidazole and theophylline, significantly inhibited ALP at concentrations which enhanced lymphocyte proliferation as measured by (3H)-thymidine uptake. DAO inhibition correlated with DNA synthesis only for IT and cimetidine. These observations suggest that ALP and DAO play a negative role in the proliferation process; however, the degree of enhancement of ConA-induced proliferation did not correlate strictly with the degree of ALP and DAO inhibition.
Metaye
T
T
Groupe de Recherches et d'Etudes d'Analogues de Médicaments (GREAM), Faculté de Médecine et de Pharmacie, Poitiers, France.
Baudry
M
M
Lalegerie
P
P
D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors*; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors*; D000818:Animals; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects*; D051379:Mice; D008811:Mice, Inbred DBA; D008934:Mitogens / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology; D013936:Thymidine / Q000378:metabolism
D008934:Mitogens; D003208:Concanavalin A; D006631:Amine Oxidase (Copper-Containing); D000469:Alkaline Phosphatase; D013936:Thymidine