Opiate-receptor interactions on single locus coeruleus neurones

J. T. Williams, R. A. North

Research output: Contribution to journalArticle

135 Scopus citations

Abstract

Intracellular recordings were made from neurones of the rat locus coeruleus (LC) which were located in a slice of pons superfused in vitro. Opioid agonists and antagonists were applied by adding them to the superfusing solution; normorphine and enkephalin analogues were also applied by ejecting a few nanoliters of a solution which contained the drugs from a pipette situated above the tissue slice. Opioid agonists hyperpolarized LC neurones. This has been shown previously to result from an increase in the membrane potassium conductance. The lowest concentration of normorphine which was effective was 30 nM, the EC50 was 1 μM, and the maximum effect was observed with 30 μM. The irreversible antagonist β-funaltrexamine (β-FNA) was used to estimate the dissociation equilibrium constants; these ranged from 9-16 μM for normorphine and [Met5enkephalin and was about 2 μM for [D-Ala2,D-Leu5]enkephalin. β-FNA also blocked the hyperpolarization caused by [D-Ala2,D-Leu5]enkephalin, ethylketacyclazocine, and [D-Ser2,D-Leu5] enkephalin-Thr. Naloxone reversibly antagonized the hyperpolarizations caused by normorphine and [D-Ala2,D-Leu5]enkephalin, with a dissociation equilibrium constant of 2 nM. It is suggested that the opioid hyperpolarization of LC neurones is mediated by a receptor having a high affinity for naloxone, previously termed a μ-receptor. The affinity of this receptor for normorphine appears to be 3 to 4 orders of magnitude lower than its affinity for naloxone.

Original languageEnglish (US)
Pages (from-to)489-497
Number of pages9
JournalMolecular pharmacology
Volume26
Issue number3
StatePublished - Dec 1 1984

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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