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.
Garnier
M
M
European Institute for Peptide Research, Institut National de la Santé de la Recherche Médicale, Unité 413, University of Rouen, Mont-Saint-Aignan, France.
Lamacz
M
M
Tonon
M C
MC
Vaudry
H
H
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