Effects of nicotine on human nasal epithelium: evidence for nicotinic receptors in non-excitable cells.
We investigated the effects of nicotine and its derivate nicotine di-d-tartrate on primary cultured human nasal epithelial cells. Both substances evoked an increase in the intracellular free calcium concentration. In the presence of extracellular Ca2+ the cytosolic Ca2+ ([Ca2+]i) increase was long lasting, whereas in the absence of external Ca2+ there was a transient increase of [Ca2+]i indicating that nicotine has an influence on Ca2+ conductances across the membranes and on intracellular Ca2+ stores. Both effects could be blocked by the nicotinic receptor antagonist methyllycaconitine (MLA). Apical or basolateral application of nicotine during transepithelial transport measurements with confluent monolayers of cultured human nasal cells resulted in a significant, reversible decrease of amiloride-sensitive sodium absorption with an apparent half-maximal blocker concentration of about 950 microM. To exclude the possibility that remnant neuronal components were responsible for the observed effects we used tetrodotoxin and verapamil to block putative neuronal channels and 4-(4-diethylamino)styryl-N-methylpyridinium iodide (4-di-2-Asp) to stain neuronal tissue. Both experimental approaches demonstrated that there were no neuronal-mediated effects. These results indicate the direct effects of nicotine on human nasal epithelium, giving the first evidence of the existence of nicotinic receptors in non-excitable cells.
Blank
U
U
Institute for Animal Physiology, Justus-Liebig-University, Giessen, Germany.
Rückes
C
C
Clauss
W
W
Weber
W M
WM
D000042:Absorption / Q000187:drug effects; D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009994:Osmolar Concentration; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C054634:methyllycaconitine; D013779:Tetrodotoxin; D009538:Nicotine; D000584:Amiloride; D012964:Sodium; D014700:Verapamil; D002118:Calcium; D000157:Aconitine