α-Tocopherol as agonist in hypoxia

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.