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 t he neurohypophysial hormones vasopressin and oxytocin was analysed in the g uinea-pig hypothalamic magnocellular neurosecretory neurons. This analysis was performed in order to understand better which population of neuroendocr ine neurons in the guinea-pig is modulated by kappa opioid receptors and it s endogenous ligand dynorphin. Extensive co-localization was observed betwe en kappa opioid receptor immunoreactivity and preprodynorphin immunoreactiv ity in neuronal cell bodies in the paraventricular and supraoptic nuclei. C ells 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 popu lation. The kappa opioid receptor and dynorphin were examined in the poster ior pituitary and both were found to be extensively distributed. Staining f or the kappa opioid receptor and dynorphin B co-localized in posterior pitu itary. In addition, immunogold electron microscopy confirmed that kappa opi oid receptor and dynorphin B immunoreactivity were found in the same nerve terminals. Ultrastructural analysis also revealed that kappa opioid recepto r immunoreactivity was associated with both nerve terminals and pituicytes. Within nerve terminals, kappa opioid receptor immunoreactivity was often a ssociated with large secretory vesicles and rarely associated with the plas ma membrane. Our data suggest that the cloned kappa opioid receptor may directly modulat e the release of vasopressin but not oxytocin in guinea-pig hypothalamic ma gnocellular neurosecretory neurons and posterior pituitary. Furthermore, we propose that this receptor is an autoreceptor in this system because our r esults demonstrate a high degree of co-localization between kappa opioid re ceptor and dynorphin peptide immunoreactivity in magnocellular nerve termin als. (C) 2000 IBRO. Published by Elsevier Science Ltd.