KAPPA-OPIOID AGONISTS INHIBIT TRANSMITTER RELEASE FROM GUINEA-PIG HIPPOCAMPAL MOSSY FIBER SYNAPTOSOMES

Opioid agonists specific for the mu, delta, and kappa-opioid receptor subtypes were tested for their ability to modulate potassium-evoked release of L-glutamate and dynorphin B-like immunoreactivity from guinea pig hippocampal mossy fiber synaptosomes. The kappa-opioid agonists U-62,066E and (-) ethylketocyclazocine, but not the [mu-agonist [D-Ala2,N-MePhe4,Gly5-ol]-enkephalin (DAGO) nor the delta-agonist [D-Pen 2,5]enkephalin (DPDE), inhibited the potassium-evoked release of L-glutamate and dynorphin B-like immunoreactivity. U-62,066E, but not DAGO or DPDE, also inhibited the potassium-evoked rise in mossy fiber synaptosomal cytosolic Ca2+ levels, indicating a possible mechanism for kappa-agonist inhibition of transmitter release. DAGO and DPDE were found to be without any effect on cytosolic Ca2+ levels or transmitter release in this preparation. The U-62,066E inhibition of the potassium-evoked rise in synaptosomal cytosolic Ca2+ levels was partially attenuated by the opioid antagonist quadazocine and insensitive to the delta-opioid specific antagonist ICI 174,864 and the mu-opioid-preferring antagonists naloxone and naltrexone. Quadazocine also reversed U-62,066E inhibition of the potassium-evoked release of L-glutamate, but not dynorphin B-like immunoreactivity. These results suggest that kappa-opioid agonists inhibit transmitter release from mossy fiber terminals through both kappa-opioid and non-kappa opioid receptor mediated mechanisms.