The phorbol ester TPA stimulates the expression of functional beta-adrenoceptors in human T lymphoblasts Molt 3.
In crude membranes from human T lymphoblasts Molt 3 cultured under standard conditions, the adenylate cyclase system was stimulated by GTP, its beta gamma-imido analogue (p[NH]ppG,) NaF and forskolin, but not by isoprenaline, prostaglandin E1 and vasoactive intestinal peptide. TPA (tumour-promoting agent phorbol ester) added at low concentration (3.2 nM) to the culture medium induced a marked increase in functional beta 2-adrenoceptors. Competition curves of [125I]cyanopindolol with the antagonist ICI 118.551 and four beta-adrenergic agonists indicated that the emergence of functional beta 2-adrenoceptors corresponded to one class of binding sites, shifting from a high-affinity state for agonists to a low-affinity state in the presence of p[NH]ppG. This expression of beta 2-adrenoceptors after a 4 h lag period depended on newly formed mRNA and protein synthesis as judged by the inhibitory effects of actinomycin D and cycloheximide. Further effects of TPA included alterations of the stimulatory G-protein Gs and/or the catalytic unit of adenylate cyclase.
Robberecht
P
P
Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Belgium.
De Neef
P
P
Buscail
L
L
Christophe
J
J
D000262:Adenylyl Cyclases / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D011943:Receptors, Adrenergic, beta / Q000032:analysis*; D013601:T-Lymphocytes / Q000032:analysis / Q000187:drug effects* / Q000201:enzymology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate