Antagonism of mu-opioid receptor-mediated inhibitions of nociceptive neurones by U50488H and dynorphin A1-13 in the rat dorsal horn.
We have studied the effects of two highly selective kappa-opioid receptor agonists, U50488H and dynorphin A1-13 on the powerful inhibitions of rat dorsal horn nociceptive neurones produced by the potent mu-opiate receptor agonist, Tyr-D-Ala-Gly-Me-Phe-Gly-ol (DAGO). Extracellular single unit recordings were made from 35 convergent neurones which could be excited by impulses in A beta- and C-fibre afferents following transcutaneous electrical stimulation of the ipsilateral hind paw. The mu- and kappa-agonists were applied directly onto the surface of the spinal cord. DAGO (0.19, 0.48 and 1.9 nmol) dose-dependently inhibited C-fibre evoked responses with little effect on A beta-evoked activity. The spinal application of dynorphin A1-13 (6.2 nmol) and U50488H (28 nmol) rapidly reversed the spinal inhibitory effect of DAGO indicating that these kappa-ligands are likely to act as mu-receptor antagonists in the rat dorsal horn.
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D004399:Dynorphins / Q000494:pharmacology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000037:antagonists & inhibitors*; D009270:Naloxone / Q000494:pharmacology; D009433:Neural Inhibition; D009619:Nociceptors / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects*; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013116:Spinal Cord / Q000187:drug effects*
D004745:Enkephalins; D010446:Peptide Fragments; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C026843:dynorphin (1-13); D004399:Dynorphins