Effects of tetrodotoxin on relaxation of pig duodenal circular muscle induced by C‐terminal fragments of cholecystokinin

1 The mechanisms by which cholecystokinin (CCK)‐C‐terminal peptides relax the isolated duodenal circular muscles of pigs were compared with mechanisms involving high potassium and electrical stimulation. 2 The relaxation (30%) induced by CCK‐8 0.263 nm was completely and non‐competitively blocked by tetrodotoxin (TTX) 0.313 μm, and was enhanced 2–2.5 times by mesaconitine 0.158 μm, tetraethylammonium (TEA) 0.597 mm and ouabain 0.136 μm. 3 The TTX sensitivity was greater for CCK‐8 and CCK‐6, than for CCK‐5 and CCK‐4. 4 High potassium (11.8–23.6 mm)‐induced, or electrically stimulated (0.3–30 Hz) relaxation showed similar characteristics except that they were not antagonized by the CCK antagonist P3‐I (168 μm). 5 Apamin (0.385–3.85 μm) enhanced relaxation induced by 10.6 mm K+, but did not affect relaxation induced by CCK‐8. 6 These results indicate that: (1) CCK‐8, K+, and transmural electrical stimulation relax duodenal circular muscles by releasing an endogenous inhibitory substance; (2) the latter two do not mediate the release of CCK; and (3) the mechanisms for relaxation by CCK‐4 are different from those of CCK‐8.