EFFECTS OF NICOTINE ON HUMAN NASAL EPITHELIUM - EVIDENCE FOR NICOTINIC RECEPTORS IN NONEXCITABLE CELLS

We investigated the effects of nicotine and its derivate nicotine di-d -tartrate on primary cultured human nasal epithelial cells. Both subst ances evoked an increase in the intracellular free calcium concentrati on. In the presence of extracellular Ca2+ the cytosolic Ca2+ ([Ca2+](i )) increase was long lasting, whereas in the absence of external Ca2there was a transient increase of [Ca2+](i) indicating that nicotine h as an influence on Ca2+ conductances across the membranes and on intra cellular Ca2+ stores. Both effects could be blocked by the nicotinic r eceptor antagonist methyllycaconitine (MLA). Apical or basolateral app lication of nicotine during transepithelial transport measurements wit h confluent monolayers of cultured human nasal cells resulted in a sig nificant, reversible decrease of amiloride-sensitive sodium absorption with an apparent half-maximal blocker concentration of about 950 mu M . To exclude the possibility that remnant neuronal components were res ponsible for the observed effects we used tetrodotoxin and verapamil t o block putative neuronal channels and 4-(4-diethylamino)styryl-N-meth ylpyridinium iodide (4-di-2-Asp) to stain neuronal tissue. Both experi mental approaches demonstrated that there were no neuronal-mediated ef fects. These results indicate the direct effects of nicotine on human nasal epithelium, giving the first evidence of the existence of nicoti nic receptors in non-excitable cells.