Selective depression of dorsal root-evoked high threshold synaptic excitation by the selective kappa opioid receptor agonist enadoline in the neonatal rat hemisected spinal cord in vitro.
The present study aimed to compare the actions of the selective kappa opioid receptor agonist enadoline (CI-977) with morphine in order to see if there is a heterogeneity of opioid receptors between spinal reflex pathways. High (C- and A-fibre evoked activity) and low (A-fibres only) intensity electrical stimulation of dorsal roots in the neonatal rat hemisected spinal cord preparation in vitro was used to distinguish between synaptic activity measured in the corresponding ventral root. Enadoline selectively depressed the high intensity-evoked EPSP with an EC50 of 7.6 nM (n = 7), contrasting with our previous finding in this preparation that morphine is an equipotent depressant of A- and C-fibre-mediated synaptic responses. The depressant effects of enadoline and morphine were reversed by naloxone giving apparent Kd values of 14 +/- 3 nM (n = 4) for enadoline-induced and 4.2 +/- 1 nM (n = 4) for morphine-induced depression. These data suggest that activation of kappa opioid receptors has a selective depressant action on C-fibre-mediated synaptic activity. Such a functional difference mediated at a subclass of opioid receptors has not been previously observed in an in vitro spinal preparation.
Department of Pharmacology, School of Medical Sciences, University Walk, Bristol, UK. L.Faber@bristol.ac.uk
E S
ES
Faber
J P
JP
Chambers
R H
RH
Evans
D000818:Animals; D000831:Animals, Newborn; D001572:Benzofurans / Q000494:pharmacology*; D066298:In Vitro Techniques; D009020:Morphine / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology
D001572:Benzofurans; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D009020:Morphine; C067110:enadoline