Nicotinic acid action on gastrointestinal smooth muscle.

The mechanism of nicotinic acid action in smooth muscle was studied by testing the drug in rat stomach fundus and descending colon using either the superfusion or perfusion technique. In the rat stomach strips nicotinic acid (or Na-nicotinate) induces concentration-dependent contractions that are drastically antagonized by indomethacin but not by the other inhibitors tested (scopolamine, phenoxybenzamine, propranolol, methysergide, pyrilamine, imidazole, anacardic acid). Reduced glutathione, on the contrary, clearly potentiates the contractile effect of nicotinic acid in the tissue. The response of the rat stomach strips to different prostanoids (PGE1, PGE2 alpha, PGF2 alpha, and PGI2) shows that only PGE2 (at a very low concentration: 14 nM) induces muscle contraction similar to that evoked by Na-nicotinate (34.4 nM). In segments of rat descending colon Na-nicotinate induces concentration-dependent contractions that are abolished by scopolamine, by hemicholinium-3 or incubation at low temperature (20 degrees C). These results provide evidence that nicotinic acid influences gastrointestinal smooth muscle by indirect mechanisms, i.e. by release of endogenous autacoids, namely prostaglandins in the stomach fundus and cholinergic transmitter in the descending colon.