No abstract

In hypoxia, but not normoxia, alpha-tocopherol (vitamin E) acts as an agonist in guinea-pig isolated colon, producing dose-dependent increases in contractile activity. This effect is mimicked by agents, vitamin K1 and phytol, which contain a structural similarity to the phytol side chain of alpha-tocopherol, but is antagonized by vitamin K3 which has a structure similar to the chromane ring of vitamin E. All of the agonist responses were blocked by atropine and potentiated by physostigmine but were unaffected by hexamethonium. However, responses to acetylcholine were not antagonized by vitamin K3 and these data suggest that alpha-tocopherol, phytol, vitamins K1 and K3 may be acting on a 'hypoxia receptor' which mediates release of acetylcholine onto muscarinic receptors.

The pharmacological action of vitamin E on the mechanical activity of isolated guinea pig colonic smooth muscle was examined in normoxic and hypoxic conditions. In hypoxia, but not normoxia, alpha-tocopherol (1-160 microM) evoked rapid concentration-dependent contractions from the colon. This was also seen with other members of the vitamin E family, and potency measurements gave EC(50) values (microM) of 10.6 +/- 0.9 for D-alpha-tocopherol, 6.0 +/- 1.2 for D-beta-tocopherol, 7.5 +/- 0.7 for D-gamma-tocopherol, and 6.1 +/- 1.5 for D-delta-tocopherol. This order of potency for the components of the vitamin differs from previously studied bioassay systems and from their antioxidant activity. A range of potent natural and synthetic antioxidants was not active in this system. Compounds with structural similarities to the side chain of vitamin E produced similar stimulatory responses and some, like phytol, were more potent than the vitamin (EC(50): 1.0 +/- 0.2 microM), whereas ring structures related to the vitamin, like Trolox C, antagonized the stimulant responses in a concentration-dependent manner. Therefore, this model system measures, directly, vitamin E-induced responses through a mechanism that does not appear to be related to the known antioxidant capacity of these agents.