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Related Experiment Videos

alpha-Tocopherol as agonist in hypoxia.

M J Kelly

    The Journal of Pharmacy and Pharmacology
    |January 1, 1986
    PubMed
    Summary
    This summary is machine-generated.

    Alpha-tocopherol (vitamin E) and related compounds stimulate guinea-pig colon contractions under hypoxia. These effects suggest a novel

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    Area of Science:

    • Pharmacology
    • Gastroenterology
    • Biochemistry

    Background:

    • Alpha-tocopherol (vitamin E) is a lipid-soluble antioxidant.
    • Its role in smooth muscle contraction, particularly under hypoxic conditions, is not well understood.
    • The guinea-pig isolated colon serves as a model for studying gastrointestinal motility.

    Purpose of the Study:

    • To investigate the contractile effects of alpha-tocopherol (vitamin E) on guinea-pig isolated colon under hypoxic conditions.
    • To explore the structural similarities and differences of related compounds (vitamin K1, K3, phytol) in mediating these effects.
    • To elucidate the potential receptor interactions and signaling pathways involved.

    Main Methods:

    • Isolated guinea-pig colon preparations were subjected to normoxic and hypoxic conditions.

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  • Dose-dependent contractile responses to alpha-tocopherol (vitamin E), vitamin K1, vitamin K3, and phytol were measured.
  • The effects of pharmacological agents like atropine, physostigmine, and hexamethonium were assessed.
  • Acetylcholine responses were also evaluated in the presence of vitamin K3.

    • Main Results:

    • Alpha-tocopherol (vitamin E) induced dose-dependent contractions in the colon under hypoxia, but not normoxia.
    • Vitamins K1 and phytol mimicked this effect, while vitamin K3 antagonized it.
    • Agonist responses were blocked by atropine and potentiated by physostigmine, indicating muscarinic receptor involvement.
    • Responses were unaffected by hexamethonium, suggesting pre-ganglionic muscarinic receptor independence.
    • Vitamin K3 did not antagonize acetylcholine responses, supporting a distinct receptor interaction.

    Conclusions:

    • Alpha-tocopherol (vitamin E) acts as a hypoxia-dependent agonist in the guinea-pig colon.
    • Structural similarities to the phytol side chain of alpha-tocopherol are crucial for agonistic activity.
    • Vitamin K3's antagonism suggests a different binding interaction, possibly at a novel 'hypoxia receptor'.
    • These findings indicate that alpha-tocopherol, phytol, and related vitamins may modulate colonic motility via a hypoxia-sensitive pathway involving acetylcholine release and muscarinic receptor activation.