A pharmacological action of vitamin E unrelated to its antioxidant capacity.
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.
Kelly
M J
MJ
School of Health and Human Sciences, Leeds Metropolitan University, Leeds, UK. m.j.kelly@leedsmet.ac.uk
Mathie
A Z
AZ
Vallance
C
C
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology; D044684:Colon, Transverse / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D000860:Hypoxia; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010836:Phytol / Q000494:pharmacology; D011748:Pyrogallol / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D013237:Stereoisomerism; D013696:Temperature; D013729:Terpenes / Q000737:chemistry / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000737:chemistry / Q000494:pharmacology*
D000975:Antioxidants; D002839:Chromans; D008689:Methacrylates; D013729:Terpenes; D011748:Pyrogallol; D010836:Phytol; C005044:hydroxyethyl methacrylate; C029141:2,2,5,7,8-pentamethyl-1-hydroxychroman; D024502:alpha-Tocopherol; D001205:Ascorbic Acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid