Agonist but not phorbol ester induced desensitization of human lymphocyte prostaglandin receptor is dependent on tubulin polymerization.
The regulation of prostaglandin stimulated cAMP accumulation in cells of the human T-cell leukemia line Jurkat was examined. Pretreatment with PGE2 (0.1-10 nM) for 2 hour caused a concentration dependent desensitization of the prostaglandin receptor. Tumor promoting phorbol esters (1-1000 nM) could also inhibit PGE2 stimulated cAMP production dose dependently. Inhibition of tubulin polymerization with colchicine or nocodazole (1 microM) eliminated prostaglandin but not phorbol ester induced desensitization of the receptor. It is concluded that agonist and phorbol ester induced desensitization are mediated by two distinct mechanisms and that tubulin polymerization appear to be required only for agonist induced desensitization of the prostaglandin receptor.
Nordstedt
C
C
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Kvanta
A
A
Fredholm
B B
BB
D001562:Benzimidazoles / Q000494:pharmacology; D001667:Binding, Competitive; D002273:Carcinogens; D003078:Colchicine / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D015458:Leukemia, T-Cell; D015739:Nocodazole; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D001562:Benzimidazoles; D002273:Carcinogens; D010703:Phorbol Esters; D011982:Receptors, Prostaglandin; D014404:Tubulin; C008876:phorbol-12,13-didecanoate; D015240:Phorbol 12,13-Dibutyrate; D000242:Cyclic AMP; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D015739:Nocodazole; D003078:Colchicine