1. The agonist sensitivity of nicotinic acetylcholine receptors in rat superior cervical ganglion (SCG) neurones was compared with that of cloned receptors expressed in Xenopus oocytes by pairwise injections of a3-,B2 or a3-,B4 neuronal nicotinic subunit combinations. 2. Agonist responses in rat SCG neurones indicated that cytisine was the most potent agonist and lobeline the least potent (rank order of potency: cytisine > dimethylphenylpiperazinium iodide (DMPP) > nicotine > ACh > carbachol > lobeline). Deneris et al. 1991) and some (e.g. a7) form functional receptors homomerically (Seguela, Wadiche, Dineley-Miller, Dani & Patrick, 1993). Rat superior cervical ganglion (SCG) neurones express mRNAs for the a3, a7, /2 and /14 subunits of the nicotinic acetylcholine receptor, with conflicting information concerning the presence of a4-1 and a5 mRNAs (Rust, Burgunder, Lauterburg & Cachelin, 1994;Mandelzys, Pie, Deneris & Cooper, 1994), but it is not known which of these subunits co-assemble to form the native functional receptors. These receptors have been extensively studied and show a number of functional as well as structural differences from those found in muscle (reviewed by Role, 1992).One way to characterize receptor subtypes is by measuring the relative potencies of a series of agonists; for example, cytisine is a potent agonist, relative to acetylcholine, for a3-,B4 receptors, but very weak for a3-/12 receptors (Luetje & Patrick, 1991; and present work). In order to cast light on the nature of the native receptors in rat sympathetic neurones, we have made parallel measurements, under comparable conditions, of agonist potency ratios on (a) neurones of the rat superior cervical ganglion, and (b) AChRs expressed in Xenopus laevis oocytes using a3-/12 or a3-,/4 subunit pairs. These

1 We have studied the eects of acute ethanol (EtOH) exposure on the agonist responses of rat neuronal nicotinic receptors expressed in Xenopus oocytes by means of voltage clamp techniques. 2 In some cells, agonist-induced current responses with the a3b4 subunit combination could be either signi®cantly potentiated or inhibited (range 25% to 237% of control response) by low ethanol concentrations (1 ± 30 mM). At high ethanol concentrations (100 ± 300 mM) robust potentiations were observed (range 135% to 305% of control). 3 The low EtOH concentration eects on the a3b4 subtype exhibited tolerance with repeated EtOH exposure. 4 In general, the a3b2, a4 ± 1b2 and a4 ± 1b4 subunit combinations were less sensitive to low concentrations of ethanol, but respectively showed potentiations of up to 178%, 226% and 154% at high EtOH concentrations. 5 The a7 homomeric receptor was also relatively insensitive at low EtOH concentrations. At high EtOH concentrations, potentiations, inhibitions or no alteration of control agonist response were observed (range 88% to 141% of control). 6 We conclude that all the neuronal nicotinic receptor subunit combinations tested here can be modulated by high concentrations of EtOH in a rapidly reversible manner. This modulation may underlie some of the behavioural eects of ethanol. The a3b4 subunit combination may be especially sensitive to modulation by low EtOH concentrations. This remarkable sensitivity and plasticity of nicotinic receptors may contribute to a process of mutual reinforcement in nicotine and alcohol addiction.

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