Investigation of the mechanism of nicotine-induced relaxation on the sheep sphincter of Oddi

Abstract

Possible mechanisms for nicotine-induced relaxation were investigated in the isolated sheep's sphincter of Oddi. Sheep's sphincter of Oddi rings were mounted in tissue bath with modified Krebs-Henseleit solution and aerated with 95% oxygen and 5% carbon dioxide. Tension was measured with isometric force transducers, and muscle relaxation was expressed as percent decrease of precontraction induced by carbachol. Nicotine (1 × 10–5 to 3 × 10–3 mol/L) produced concentration-dependent relaxation on sphincter of Oddi precontracted by carbachol (10–6 mol/L). Nicotine-induced relaxation was 72.8 ± 4.2% of precontraction with carbachol (10–6 mol/L) (mean pD2 value, 3.76 ± 0.05 mol/L). Nicotine-induced relaxation was not affected by N(w)-nitro L-arginine methyl ester (L-NAME) (3 × 10–5 mol/L), methylene blue (10–5 mol/L), indomethacin (10–5 mol/L), hexamethonium (10–5 mol/L), glibenclamide (10–5 mol/L), 4-aminopyridine (10–3 mol/L), tetraethylammonium (3 × 10–4 mol/L), clotrimazole (10–6 mol/L), 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) (10–6 mol/L), and anthracene-9-carboxylate (9-AC) (10–6 mol/L), but potentiated by bupivacain (10–5 mol/L). A calcium-antagonizing effect of nicotine was not observed. The results suggest that nicotine-induced relaxation of the sheep's sphincter of Oddi is not mediated by the release of prostaglandins, nitric oxide (NO), or a related substance; by the activation of potassium channels or chloride channels; or by the stimulation of nicotinic cholinoceptors. Potentiation of the nicotine-induced relaxation by bupivacain indicates that blockade of sodium channels may play a role in this relaxation.Key words: nicotine, sphincter of Oddi, relaxation.