Functional heterogeneity of nicotinic receptors in the avian lateral spiriform nucleus detected with trimethaphan

WR Weaver, KM Wolf and VA Chiappinelli

Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Missouri 63104.

We have examined an excitatory response mediated by nicotinic acetylcholine receptors located on the somata and/or dendrites of chick lateral spiriform neurons. On the basis of pharmacological and anatomical studies, these receptors belong to a subgroup of nicotinic receptors termed high affinity nicotine receptors, because they exhibit a high affinity for nicotinic agonists but little or no sensitivity to alpha- or kappa-bungarotoxin. We now report physiological evidence that high affinity nicotine receptors in the lateral spiriform nucleus are heterogeneous. Intracellular recording in brain slices was used to examine the pharmacological characteristics of nicotinic responses in individual lateral spiriform neurons. Nicotinic responses to brief applications of carbachol were inhibited by trimethaphan, dihydro-beta- erythroidine, or d-tubocurarine. Trimethaphan was unusual, in that a wide range of concentrations (< or = 50 microM to > 500 microM) were required to block this nicotinic response in different neurons. To quantitate the inhibition observed with trimethaphan and dihydro-beta- erythroidine, dose-response curves were generated in superfusion studies using a wide range of concentrations of both agonist (3-3000 microM carbachol in the presence of 1 microM atropine and 0.25 microM tetrodotoxin) and antagonists (10-500 microM trimethaphan or 0.1-3 microM dihydro-beta-erythroidine). The data yielded an EC50 of 25 +/- 5 microM for carbachol, with a Hill coefficient of 1.4 +/- 0.1 (mean +/- standard error; n = 8). In the case of dihydro-beta-erythroidine, a narrow range of Ki values was obtained (0.09-0.16 microM; n = 5). In contrast, Ki values for trimethaphan varied over a 15-fold concentration range (4-66 microM; n = 17), demonstrating that trimethaphan showed selectivity for different receptor subtypes found in the lateral spiriform nucleus. For both antagonists, the data indicate a competitive mode of inhibition.

Volume 46, Issue 5, pp. 993-1001, 11/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics