Effects of beta-adrenergic receptor activation, cholera toxin and forskolin on human natural killer cell function.
Membranes from highly purified natural killer (NK) cells were ADP-ribosylated by treatment with cholera toxin (CTX). CTX resulted in a single band of specific 32P incorporation at Mr 43,600. CTX treatment of intact NK cells caused a 9-fold increase in cyclic AMP (cAMP) concentrations. Pretreatment of NK cells with CTX diminished their ability to lyse K562 tumour cells by up to 79%. Forskolin treatment elevated NK cell cAMP levels 8-fold and decreased lysis of K562 cells by up to 45%. Adrenaline and isoprenaline (isoproterenol) both inhibited lysis of K562 cells by approx. 35% and elevated cAMP by at least 2.5-fold, and their inhibition of lysis was reversed by propranolol. These data suggest that the stimulatory guanine-nucleotide-binding protein GS coupled to beta-adrenergic receptors is involved in transducing signals which inhibit NK cell lysis of tumour cells. CTX and forskolin also diminish the ability of NK cells to bind K562 cells (binding is necessary for lysis). This suggests that the NK-cell receptor(s) for the tumour cell may be altered as a consequence of cAMP-mediated events or by activation of GS.
Whalen
M M
MM
Department of Medicine, University of New Mexico School of Medicine, Albuquerque 87131.
Bankhurst
A D
AD
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D008565:Membrane Proteins / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D008565:Membrane Proteins; D010761:Phosphorus Radioisotopes; D011943:Receptors, Adrenergic, beta; D009243:NAD; D005576:Colforsin; D000246:Adenosine Diphosphate Ribose; D000001:Calcimycin; D002772:Cholera Toxin; D000242:Cyclic AMP; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate; D004837:Epinephrine