The kappa opioid receptor and dynorphin co-localize in vasopressin magnocellular neurosecretory neurons in guinea-pig hypothalamus

The relationship between the cloned kappa opioid receptor, dynorphin, and the neurohypophysial hormones vasopressin and oxytocin was analysed in the guinea-pig hypothalamic magnocellular neurosecretory neurons. This analysis was performed in order to understand better which population of neuroendocrine neurons in the guinea-pig is modulated by kappa opioid receptors and its endogenous ligand dynorphin. Extensive co-localization was observed between kappa opioid receptor immunoreactivity and preprodynorphin immunoreactivity in neuronal cell bodies in the paraventricular and supraoptic nuclei. Cells positive for either the kappa opioid receptor or both the kappa opioid receptor and preprodynorphin were restricted to the vasopressin expressing neuronal population and not found in the oxytocin expressing neuronal population. The kappa opioid receptor and dynorphin were examined in the posterior pituitary and both were found to be extensively distributed. Staining for the kappa opioid receptor and dynorphin B co- localized in posterior pituitary. In addition, immunogold electron microscopy confirmed that kappa opioid receptor and dynorphin B immunoreactivity were found in the same nerve terminals. Ultrastructural analysis also revealed that kappa opioid receptor immunoreactivity was associated with both nerve terminals and pituicytes. Within nerve terminals, kappa opioid receptor immunoreactivity was often associated with large secretory vesicles and rarely associated with the plasma membrane. Our data suggest that the cloned kappa opioid receptor may directly modulate the release of vasopressin but not oxytocin in guinea-pig hypothalamic magnocellular neurosecretory neurons and posterior pituitary. Furthermore, we propose that this receptor is an autoreceptor in this system because our results demonstrate a high degree of co-localization between kappa opioid receptor and dynorphin peptide immunoreactivity in magnocellular nerve terminals. (C) 2000 IBRO.