Actions of mu, delta and kappa opioid agonists and antagonists on mouse primary afferent neurons in culture

J Pharmacol Exp Ther. 1987 Oct;243(1):258-63.

Abstract

The effects of selective mu, delta and kappa opioid agonists and antagonists were studied on somatic calcium-dependent action potentials recorded from mouse dorsal root ganglion (DRG) neurons grown in dissociated cell culture. The mu selective agonist, PL 017, and the delta selective agonist, [D-Pen2, L-Pen5] enkephalin (DPLPE), reduced action potential duration of a subpopulation (21/56) of DRG neurons. Leucine-enkephalin reduced action potential duration of all neurons sensitive to PL 017 or DPLPE, whereas 85% of neurons responding to leucine-enkephalin responded to either PL 017 or DPLPE. Only 15% of neurons responded to both PL 017 and DPLPE. There was no significant difference in the response to PL 017 or DPLPE when compared to leucine-enkephalin. In another experiment, the kappa selective agonist dynorphin A (DYN A), PL 017 and DPLPE reduced action potential duration of a subpopulation (15/67) of DRG neurons. There was a heterogeneous response among neurons to PL 017, DPLPE and DYN A inasmuch as 21.4% of neurons responded to all three agonists, 35.7% responded to PL 017 and DYN A, 35.7% responded only to PL 017 and 7.1% responded only to DYN A. Responses to the mu selective agonist PL 017 were antagonized by the reversible opioid antagonist naloxone and the selective mu antagonist SMS 201-995 in a concentration-dependent fashion. Responses to PL 017 were not altered by the selective delta antagonist ICI 174864. Responses to PL 017 were reduced by the irreversible, selective mu antagonists beta-funaltrexamine and naloxonazine in a concentration-dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Afferent Pathways / drug effects
  • Afferent Pathways / physiology*
  • Animals
  • Cells, Cultured
  • Ganglia, Spinal / physiology
  • Mice
  • Narcotics / pharmacology*
  • Neurons / physiology*
  • Receptors, Opioid / physiology*
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Spinal Cord / physiology
  • Structure-Activity Relationship

Substances

  • Narcotics
  • Receptors, Opioid
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu