OPIATE-RECEPTOR INTERACTIONS ON SINGLE LOCUS COERULEUS NEURONS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 26  (3) , 489-497
Abstract
Intracellular recordings were made from neurons 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 anlogs were also applied by ejecting a few nl of a solution which contained the drugs from a pipette situated above the tissue slice. Opioid agonists hyperpolarized LC neurons. This results from an increase in the membrane K+ conductance. The lowest concentration of normorphine which was effective was 30 nM, the EC50 [median effective concentration] was 1 .mu.M, and the maximum effect was observed with 30 .mu.M. The irreversible antagonist .beta.-funaltrexamine (.beta.-FNA) was used to estimate the dissociation equilibrium constants; these ranged from 9-16 .mu.M for normorphine and [Met5]enkephalin and was about 2 .mu.M for [D-Ala2,D-Leu5]enkephalin. .beta.-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. The opioid hyperpolarization of LC neurons may be mediated by a receptor having a high affinity for naloxone, previously termed a .mu.-receptor. The affinity of this receptor for normorphine appears to be 3-4 orders or magnitude lower than its affinity for naloxone.