Reduced responsiveness of adenylate cyclase to forskolin in human lymphoma cells.
The beta 2-adrenergic transmembrane signal transduction was investigated in malignant B-cells from 15 patients with low grade non-Hodgkin's lymphoma as compared with normal lymphocytes of seven healthy adults. The number of beta 2-adrenoceptors and the response of adenylate cyclase (AC) to isoproterenol were slightly decreased in lymphoma cells. The responsiveness of AC to forskolin was 8-fold lower in lymphoma cells, whereas the response to cholera toxin showed no difference. These findings demonstrate an impairment of the beta 2-adrenergic signal transduction in low grade lymphoma cells that particularly affects the function of AC. The comparison with forskolin resistant mutants of an adrenocortical tumor cell line, Y1 (Schimmer et al., J Biol Chem 262: 15521-15526, 1987), suggests that the availability of functional active alpha subunits of stimulatory G proteins (Gs) might be reduced in human B-cell lymphoma, although other mechanisms known to inhibit the AC activity might be involved.
Hallek
M
M
Medizinische Klinik, Klinikum Innenstadt, University of Munich, Germany.
Kamp
T
T
Haen
E
E
Göhly
U
U
Emmerich
B
B
Remien
J
J
D000067956:Adenylyl Cyclase Inhibitors; D000368:Aged; D001402:B-Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D001665:Binding Sites; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008228:Lymphoma, Non-Hodgkin / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000067956:Adenylyl Cyclase Inhibitors; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; C047975:cyanopindolol; D002772:Cholera Toxin; D010869:Pindolol; D000242:Cyclic AMP; D007545:Isoproterenol