Stimulus-dependent translocation of kappa opioid receptors to the plasma membrane

We examined the cellular and subcellular distribution of the cloned kappa o pioid receptor (KOR1) and its trafficking to the presynaptic plasma membran e in vasopressin magnocellular neurosecretory neurons. We used immunohistoc hemistry to show that KOR1 immunoreactivity (IR) colocalized with vasopress in-containing cell bodies, axons, and axon terminals within the posterior p ituitary, Ultrastructural analysis revealed that a major fraction of KOR1-I R was associated with the membrane of peptide-containing large secretory ve sicles. KOR1-IR was rarely associated with the plasma membrane in unstimula ted nerve terminals within the posterior pituitary. A physiological stimulu s (salt-loading) that elicits vasopressin release also caused KOR1-IR to tr anslocate from these vesicles to the plasma membrane. After stimulation, th ere was a significant decrease in KOR1-IR associated with peptide-containin g vesicles and a significant increase in KOR1-IR associated with the plasma membrane. This stimulus-dependent translocation of receptors to the presyn aptic plasma membrane provides a novel mechanism for regulation of transmit ter release.