Modulation of acetylcholine‐induced contractions of the rat anococcygeus muscle by activation of nitrergic nerves

Acetylcholine‐induced contractions of the rat isolated anococcygeus muscle were blocked by atropine (0.1 μm), slightly enhanced by hexamethonium (0.1 mm) and tetrodotoxin (1 μm), but little affected by prazosin (0.1 μm). In the presence of the α₂‐adrenoceptor agonist, UK14304, which raised the tone of the muscle, acetylcholine had a biphasic effect consisting of an initial relaxation followed by a contraction. Atropine (0.1 μm) enhanced the relaxant component and abolished the contractile component of the response, whereas tetrodotoxin, ω‐conotoxin GVIA or hexamethonium abolished or greatly reduced the relaxant component. The nitric oxide synthesis inhibitor N^G‐nitro‐l‐arginine methyl ester (l‐NAME, 100 μm) increased acetylcholine‐induced contractions in the absence of UK14304 and markedly reduced the relaxant component to acetylcholine in the presence of UK14304. The effects of l‐NAME were annulled by l‐arginine (300 μm). The results suggest that acetylcholine acts concurrently on muscarinic receptors of the smooth muscle to cause contraction and nicotinic receptors of nitrergic nerves to cause relaxation. The observed response is the resultant of these two opposing effects and depends also on the prevailing tone. 1993 British Pharmacological Society