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Kappa opioid agonists inhibit transmitter release from guinea pig hippocampal mossy fiber synaptosomes

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Abstract

Opioid agonists specific for the μ, δ, and κ 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 κ opioid agonists U-62,066E and (−) ethylketocyclazocine, but not the μ agonist [D-Ala2,N-MePhe4,Gly5-ol]-enkephalin (DAGO) nor the δ 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 κ 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 δ-opioid specific antagonist ICI 174,864 and the μ 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 κ opioid agonists inhibit transmitter release from mossy fiber terminals through both κ opioid and non-κ opioid receptor mediated mechanisms.

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  1. Department of Anatomy and Cell Biology, East Carolina University, School of Medicine, 27858-4354, Greenville, NC

    Robert L. Gannon & David M. Terrian PhD

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  1. Robert L. Gannon
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Gannon, R.L., Terrian, D.M. Kappa opioid agonists inhibit transmitter release from guinea pig hippocampal mossy fiber synaptosomes. Neurochem Res 17, 741–747 (1992). https://doi.org/10.1007/BF00969007

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