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Benzodiazepines decrease norepinephrine release from rat pineal nerves by acting on peripheral type binding sites.

P R Lowenstein, C González Solveyra, M I Keller Sarmiento

    Acta Physiologica Et Pharmacologica Latinoamericana : Organo De La Asociacion Latinoamericana De Ciencias Fisiologicas Y De La Asociacion Latinoamericana De Farmacologia
    |January 1, 1985
    PubMed
    Summary
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    Benzodiazepine (BZP) binding sites in rat pineal glands influence neurotransmitter release and melatonin synthesis. These peripheral BZP sites significantly reduce transmitter release, impacting melatonin production more than direct postsynaptic stimulation.

    Area of Science:

    • Neuropharmacology
    • Endocrinology
    • Chronobiology

    Background:

    • Benzodiazepines (BZP) are known for their effects on the central nervous system.
    • The presence and function of BZP binding sites in peripheral tissues, such as the pineal gland, are less understood.
    • The pineal gland plays a crucial role in melatonin synthesis and circadian rhythm regulation.

    Purpose of the Study:

    • To investigate the presence and characteristics of BZP binding sites in rat pineal homogenates.
    • To determine the effect of BZP on neurotransmitter release from sympathetic nerves innervating the pineal gland.
    • To examine the influence of BZP on melatonin synthesis in rat pineal explants, particularly after denervation.

    Main Methods:

    • Radioligand binding assays using 3H-flunitrazepam (FNZP) to characterize BZP binding sites in rat pineal homogenates.

    Related Experiment Videos

  • Measurement of norepinephrine release from pineal explants stimulated by high potassium in the presence of various BZP.
  • Quantification of melatonin content in pineal explants incubated with BZP, including experiments on denervated glands (SCGx).

    • Main Results:

    • A single population of BZP binding sites was identified in rat pineal homogenates with specific affinity orders for different BZP.
    • Bilateral superior cervical ganglionectomy (SCGx) reduced the number of BZP binding sites in the pineal gland.
    • BZP (Ro 5-4864, diazepam) significantly decreased K+-evoked norepinephrine release and increased melatonin content in pineal explants, with reduced effects in denervated glands.

    Conclusions:

    • Peripheral BZP binding sites in rat pineal sympathetic nerves modulate neurotransmitter release.
    • BZP binding sites contribute to the regulation of pineal melatonin synthesis, with a significant effect on transmitter release.
    • The impact of BZP on transmitter release is considerably greater than its postsynaptic effect on melatonin synthesis.