Mechanisms of mitogen-activated protein kinase activation by nicotine in small-cell lung carcinoma cells.
We have previously reported that nicotine stimulates cell proliferation of three small-cell lung carcinoma (SCLC) cell lines by activating nicotinic receptors of the neuronal type. Here we report that, in the GLC-8 SCLC cell line, nicotine stimulates mitogen-activated protein (MAP) kinase activity in a concentration- and time-dependent manner (ED50 = 10 nM). The nicotine effect was antagonized by mecamylamine, an antagonist specific for neuronal nicotinic receptors. The absence of extracellular Ca2+, or pretreatment with pertussis toxin or the tyrosine kinase inhibitor genistein inhibited the action of nicotine on MAP kinase. Moreover, supernatants from nicotine-stimulated cells transferred to cells pretreated with mecamylamine were still capable of activating MAP kinase. On the other hand, the same supernatants transferred to cells pretreated with mecamylamine and pertussis toxin or genistein failed to activate MAP kinase. These findings suggest that nicotine elicits its stimulatory effect on MAP kinase in SCLC cells indirectly by inducing the production and/or release of a factor which then acts via a pertussis toxin- and tyrosine kinase-sensitive route.
Cattaneo
M G
MG
Department of Pharmacology, School of Medicine, University of Milano, Via Vanvitelli 32, 20129, Milano, Italy.
D'atri
F
F
Vicentini
L M
LM
D019898:Autocrine Communication; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology*; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D037342:Pertussis Toxin; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011950:Receptors, Cholinergic / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011950:Receptors, Cholinergic; D010566:Virulence Factors, Bordetella; D008464:Mecamylamine; D009538:Nicotine; D019833:Genistein; D037342:Pertussis Toxin; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium