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 microM, and was enhanced 2-2.5 times by mesaconitine 0.158 microM, tetraethylammonium (TEA) 0.597 mM and ouabain 0.136 microM. 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 microM). 5. Apamin (0.385-3.85 microM) 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.