Altered beta-adrenoceptor function associated to protein kinase C activation in hyperproliferative T lymphocytes.
beta-Adrenoceptor (betaAR) expression and function as well as its modulation via intracellular transduction signals, were analyzed on the T cell lymphoma BW5147. Independently to the kinetic of proliferation and relative to the number of receptors displayed in normal T lymphocytes, BW5147 cells displayed a decreased number of betaAR, uncoupled to adenylate cyclase, but coupled to protein kinase C stimulation. This last effect was impaired by a beta-antagonist and by blockers of the enzymatic pathways involved in T lymphocyte proliferation, inducing a recovery of betaAR sites. Down-regulation of betaAR would implicate the loss of a negative neuroimmune control mechanism for lymphocyte proliferation. The coupling of the remaining sites to a positive signal for cellular activation, would contribute to establish an hyperproliferative state.
Cremaschi
G A
GA
Centro de Estudios Farmacológicos y Botánicos (CEFYBO), CONICET, Serrano 669, 1414, Buenos Aires, Argentina. grace@cefybo.edu.ar
Genaro
A M
AM
Cazaux
C A
CA
Anesini
C
C
Wald
M
M
Borda
T
T
Sterin-Borda
L
L
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D016399:Lymphoma, T-Cell; D008301:Maleimides / Q000494:pharmacology; D015213:Neuroimmunomodulation / Q000276:immunology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000201:enzymology* / Q000276:immunology; D014407:Tumor Cells, Cultured
D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D011943:Receptors, Adrenergic, beta; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D007545:Isoproterenol; C070515:bisindolylmaleimide I