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 m elanotrophs, nicotine stimulates alpha-melanocyte stimulating hormone (alpha-MSH) release through a noncholinergic mechanism. In the study r eported here, we investigated the intracellular events that mediate th e response of frog melanotrophs to nicotine. Nicotine was capable of s timulating alpha-MSH release in the absence of Ca2+ and/or Na+ in the extracellular medium. A short pulse of nicotine induced a rapid and tr ansient increase of cytosolic free Ca2+ concentration ([Ca2+](i)). The effect of nicotine on Ca2+ mobilization was not affected in the absen ce of Na+ and Ca2+ in the extracellular medium, indicating that the ni cotine-evoked increase in [Ca2+](i) did not result from Na+ or Ca2+ in flux. Nicotine induced both an increase in inositol trisphosphate and a reduction in phosphaditylinositol bisphosphate concentrations but di d not affect cAMP production. The present results indicate that nicoti ne-induced stimulation of alpha-MSH release in frog melanotrophs can b e explained by activation of inositolphospholipid breakdown and mobili zation of inositol trisphosphate dependent intracellular Ca2+ pools. T hese data provide evidence for the existence of an unusual type of non cholinergic nicotine receptor positively coupled to phospholipase C.