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Coexisting peptides in hypothalamic neuroendocrine systems: some functional implications.

C A Bondy1, M H Whitnall, L S Brady

  • 1Laboratory of Neurochemistry, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.

Cellular and Molecular Neurobiology
|December 1, 1989
PubMed
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Copeptides like dynorphin, cholecystokinin (CCK), and corticotropin-releasing hormone (CRH) modulate oxytocin and vasopressin secretion from the rat neurohypophysis. These peptides, coreleased with major hormones, exhibit distinct regulatory effects on hormone release via specific receptor interactions.

Area of Science:

  • Neuroendocrinology
  • Molecular Endocrinology
  • Cellular Neuroscience

Background:

  • The hypothalamic-neurohypophysial system releases oxytocin and vasopressin, coexisting with various "copeptides" in nerve terminals.
  • Evidence suggests corelease of these copeptides with major magnocellular hormones, implying regulatory roles.

Purpose of the Study:

  • To investigate the effects of three specific copeptides—dynorphin, cholecystokinin (CCK), and corticotropin-releasing hormone (CRH)—on oxytocin and vasopressin secretion.
  • To elucidate the mechanisms and receptor locations mediating these copeptide actions in vitro.

Main Methods:

  • Utilized isolated rat neural lobe and neurointermediate lobe preparations for in vitro studies.
  • Examined the effects of dynorphin, CCK, and CRH on basal and stimulated secretion of oxytocin and vasopressin.

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  • Investigated the role of specific receptors, protein kinase C, and extracellular calcium in mediating copeptide effects.

    • Main Results:

    • Dynorphin inhibits oxytocin secretion via kappa-opiate receptors in the neural lobe, with naloxone enhancing release proportionally to vasopressin/dynorphin.
    • CCK stimulates oxytocin and vasopressin secretion independently of electrical stimulation and Ca2+, involving protein kinase C.
    • CRH and intermediate lobe peptides (alpha/gamma-MSH) stimulate hormone secretion from combined neurointermediate lobes, with CRH acting on the intermediate lobe, not the neural lobe.

    Conclusions:

    • Dynorphin, CCK, and CRH act as significant modulators of oxytocin and vasopressin release through distinct pathways.
    • CCK and intermediate lobe peptides activate protein kinase C signaling, while dynorphin acts via kappa-opiate receptors.
    • CRH neurons, particularly those coexpressing vasopressin, show stress-dependent activation, suggesting differential regulatory inputs.