Functional characterization of a nonclassical nicotine receptor associated with inositolphospholipid breakdown and mobilization of intracellular calcium pools.
Classical nicotinic receptors are neurotransmitter-gated channels that, upon activation by acetylcholine, induce the opening of an intrinsic cationic channel. We have recently observed that, in frog pituitary melanotrophs, nicotine stimulates alpha-melanocyte-stimulating hormone (alpha-MSH) release through a noncholinergic mechanism. In the study reported here, we investigated the intracellular events that mediate the response of frog melanotrophs to nicotine. Nicotine was capable of stimulating alpha-MSH release in the absence of Ca2+ and/or Na+ in the extracellular medium. A short pulse of nicotine induced a rapid and transient increase of cytosolic free Ca2+ concentration ([Ca2+]i). The effect of nicotine on Ca2+ mobilization was not affected in the absence of Na+ and Ca2+ in the extracellular medium, indicating that the nicotine-evoked increase in [Ca2+]i did not result from Na+ or Ca2+ influx. Nicotine induced both an increase in inositol trisphosphate and a reduction in phosphaditylinositol bisphosphate concentrations but did not affect cAMP production. The present results indicate that nicotine-induced stimulation of alpha-MSH release in frog melanotrophs can be explained by activation of inositolphospholipid breakdown and mobilization of inositol triphosphate-dependent intracellular Ca2+ pools. These data provide evidence for the existence of an unusual type of noncholinergic nicotine receptor positively coupled to phospholipase C.
European Institute for Peptide Research, Institut National de la Santé de la Recherche Médicale, Unité 413, University of Rouen, Mont-Saint-Aignan, France.
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Garnier
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Lamacz
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Tonon
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Vaudry
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002451:Cell Compartmentation; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010902:Pituitary Gland / Q000378:metabolism; D011898:Ranidae; D011978:Receptors, Nicotinic / Q000378:metabolism*; D015398:Signal Transduction; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D000521:alpha-MSH / Q000378:metabolism
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011978:Receptors, Nicotinic; D013729:Terpenes; D000521:alpha-MSH; D019284:Thapsigargin; D009538:Nicotine; D000242:Cyclic AMP; D002118:Calcium