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-Pen2,5]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.