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RECEPTORS AND SIGNAL TRANSDUCTION
1Instituto "Teófilo Hernando", 2Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid; and 3Servicio de Farmacología Clínica, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain
Submitted 23 November 2008 ; accepted in final form 5 February 2009
We have investigated here whether a preconditioned stimulation of nicotinic and muscarinic receptors augmented the catecholamine release responses elicited by supramaximal 3-s pulses of 100 µM acetylcholine (100ACh) or 100 mM K+ (100K+) applied to fast-perifused bovine adrenal chromaffin cells. Threshold concentrations of nicotine (1–3 µM) that caused only a tiny secretion did, however, augment the responses elicited by 100ACh or 100K+ by 2- to 3.5-fold. This effect was suppressed by mecamylamine and by Ca2+ deprivation, was developed with a half-time (t1/2) of 1 min, and was reversible. The nicotine effect was mimicked by threshold concentrations of ACh, choline, epibatidine, and oxotremorine-M but not by methacholine. Threshold concentrations of K+ caused lesser potentiation of secretion compared with that of threshold nicotine. The data are compatible with an hypothesis implying 1) that continuous low-frequency sympathetic discharge places chromaffin cells at the adrenal gland in a permanent "hypersensitive" state; and 2) this allows an explosive secretion of catecholamines by high-frequency sympathetic discharge during stress.
nicotinic receptors; chromaffin cells; choline; acetylcholine; methacholine; potassium; catecholamine release
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