Nicotine-induced membrane perturbation of intact human granulocytes spin-labeled with 5-doxylstearic acid. Correlation with chemotaxis.
The effects of nicotine on intact human granulocytes were examined, using 5-doxylstearic acid as a spin probe. At micromolar concentrations, (-)-nitocine produces a membrane perturbation in granulocytes not observable with oriented lipid bilayers. The effect, which is stereoselective for the (-)-isomer, occurs at concentrations of nicotine that bind to noncholinergic nicotine receptors on granulocytes and which are present in the blood after smoking. At comparable concentrations, (-)-nicotine modulates granulocyte chemotaxis towards a chemotactic peptide in a stereospecific and dose-dependent manner. Cotinine, the major metabolite of nicotine, does not bind to the receptor, does not produce the membrane perturbation observed with nicotine, and has no effect on chemotaxis. These results suggest that (-)-nicotine present in the blood after smoking binds to a receptor on granulocytes, perturbs granulocyte membranes and modulates chemotaxis.
D002462:Cell Membrane / Q000187:drug effects*; D002634:Chemotaxis, Leukocyte; D003367:Cotinine / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D006098:Granulocytes / Q000187:drug effects*; D006801:Humans; D009538:Nicotine / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000378:metabolism; D013113:Spin Labels / Q000378:metabolism*; D013237:Stereoisomerism
D003497:Cyclic N-Oxides; D011978:Receptors, Nicotinic; D013113:Spin Labels; C005072:5-doxylstearic acid; D009538:Nicotine; D003367:Cotinine