Skip to main content
SpringerLink
Log in

Blockade of α2-adrenoceptors increases opioid μ-receptor-mediated inhibition of the firing rate of rat locus coeruleus neurones

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

In pontine slices of the rat brain, the frequency of spontaneous action potentials of locus coeruleus (LC) neurones was recorded extracellularly. Noradrenaline 0.1–100 μmol/l, UK 14,304 0.01–100 nmol/l, [Met5]-enkephalin 1–10,000 nmol/l and [D-Ala2, D-Leu5]enkephalin 0.1–1,000 nmol/l, all depressed the firing rate. Rauwolscine 1 μmol/l antagonized the effects of both noradrenaline and UK 14,304, but potentiated the effects of [Met']enkephalin and [D-Ala2, D-Leu5]enkephalin. Idazoxan 1 μmol/l acted in a similar manner. Prazosin 1 μmol/l did not change the effects of either noradrenaline or [Met5]enkephalin. Naloxone 0.1 μmol/l antagonized both [Met']enkephalin and [D-Ala2, D-Leu5]enkephalin, but failed to alter the effects of either noradrenaline or UK 14,304. Rauwolscine, idazoxan and prazosin, all 1 μmol/l, as well as naloxone 0.1 μmol/l, did not influence the firing rate when given alone. Desipramine 1 μmol/l inhibited the discharge of action potentials in a rauwolscine-antagonizable manner. Noradrenaline 10 μmol/l produced the same depression of firing, both in the presence of noradrenaline 1 μmol/l and [Met5]enkephalin 0.03 μmol/l. Likewise, the effect of [Met5]enkephalin 0.3 μmol/l was the same, irrespective of whether it was added to a medium containing [Met5]enkephalin 0.03 μmol/l or noradrenaline 1 μmol/l. The spontaneous activity of LC neurones is inhibited by somatic α2-adrenoceptors and opioid μ-receptors. We suggest that the two receptors interact with each other at a site located between themselves and not in the subsequent common signal transduction system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aghajanian GK, VanderMaelen CP (1982) α2-Adrenoceptor-mediated hyperpolarization of locus coerulcus neurones: intracellular studies in vivo. Science 215:1394–1396

    Google Scholar 

  • Aghajanian GK, Wang YY (1986) Pertussis toxin blocks the outward currents evoked by opiate and α2-agonists in locus coeruleus neurons. Brain Res 371:390–394

    Google Scholar 

  • Aghajanian GK, Wang YY (1987) Common α2- and opiate effector mechanisms in the locus coeruleus: intracellular studies in brain slices. Neuropharmacology 26:793–799

    Google Scholar 

  • Allgaier C, Daschmann B, Sieverling J, Hertting G (1989) Presynaptic κ-opioid receptors on noradrenergic nerve terminals couple to G proteins and interact with the α2-adrenoceptors. J Neurochem 53:1629–1635

    Google Scholar 

  • Cederbaum JM, Aghajanian GK (1977) Catecholamine receptors of locus coeruleus neurones: pharmacological characterization. Eur J Pharmacol 44:375–385

    Google Scholar 

  • Doxey JC, Smith CFC, Walker JM (1977) Selectivity of blocking agents for pre- and postsynaptic α-adrenoceptors. Br J Pharmacol 60:91–96

    Google Scholar 

  • Doxey JC, Roach AG, Smith CFC (1983) Studies on RX 781094: a selective, potent and specific antagonist of α2-adrenoceptors. Br J Pharmacol 78:489–505

    Google Scholar 

  • Doxey JC, Lane AC, Roach AG, Smith CFC, Walter DS (1985) Selective α2-adrenoceptor agonists and antagonists. In: Szabadi E, Bradshaw CM, Nahorski SR (eds) Pharmacology of adrenoceptors. VCH, Weinheim, pp 13–22

    Google Scholar 

  • Egan TM, Henderson G, North RA, Williams JT (1983) Noradrenaline-mediated synaptic inhibition in rat locus coeruleus neurones. J Physiol 345:477–488

    Google Scholar 

  • Foote SL, Aston-Jones G, Bloom FE (1980) Impulse activity of locus coeruleus neurones in awake rats and monkeys is a function of sensory stimulation and arousal. Proc Natl Acad Sci USA 77:3033–3037

    Google Scholar 

  • Foote SL, Bloom FE, Aston-Jones G (1983) Nucleus locus coeruleus: new evidence of anatomical and physiological specifity. Physiol Rev 63:844–915

    Google Scholar 

  • Furchgott RF (1972) The classification of adrenoceptors (adrenergic receptors). An evaluation from the standpoint of receptor theory. In: Blaschko H, Muscholl E (eds) Catecholamines. Handbook of Experimental Pharmacology Vol 33. Springer, Berlin Heidelberg, pp 283–335

    Google Scholar 

  • Hagan RM, Hughes IE (1984) Opioid receptor sub-types involved in the control of transmitter release in cortex of the brain of the rat. Neuropharmacology 23:491–495

    Google Scholar 

  • Henderson G, Pepper CM, Shefner SA (1982) Electrophysiological properties of neurones contained in the locus coeruleus and mesencephalic nucleus of the trigeminal nerve in vitro. Exp Brain Res 45:29–37

    Google Scholar 

  • Illes P (1986) Mechanisms of receptor-mediated modulation of transmitter release in noradrenergic, cholinergic and sensory neurones. Neuroscience 17:909–928

    Google Scholar 

  • Illes P (1989) Modulation of transmitter and hormone release by multiple neuronal opioid receptors. Rev Physiol Biochem Pharmacol 112:139–233

    Google Scholar 

  • Illes P, Regenold JT (1990) Interaction between neuropeptide Y and noradrenaline on central catecholamine neurons. Nature 344:62–63

    Google Scholar 

  • Illes P, Weber HD, Neuburger J, Bucher B, Regenold JT, Nörenberg W (1990) Receptor interactions at noradrenergic neurones. In: Kalsner S, Westfall TC (eds) Presynaptic receptors and the question of autoregulation of neurotransmitter release. Ann NY Acad Sci (in press)

  • Jackisch R, Geppert M, Illes P (1986) Characterization of opioid receptors modulating noradrenaline release in the hippocampus of the rabbit. J Neurochem 46:1802–1810

    Google Scholar 

  • Langer SZ (1981) Presynaptic regulation of the release of catecholamines. Pharmacol Rev 32:337–361

    Google Scholar 

  • Limberger N, Späth L, Hölting T, Starke K (1986) Mutual interaction between presynaptic α2-adrenoceptors and opioid к-receptors at the noradrenergic axons of rabbit brain cortex. Naunyn-Schmiedeberg's Arch Pharmacol 334:166–171

    Google Scholar 

  • Limberger N, Singer EA, Starke K (1988a) Only activated but not non-activated presynaptic a2-autoreceptors interfere with neighbouring presynaptic receptor mechanisms. Naunyn-Schmiedeberg's Arch Pharmacol 338:62–67

    Google Scholar 

  • Limberger N, Späth L, Starke K (1988b) Presynaptic α2-adrenoceptor, opioid x-receptor and adenosine A1-receptor interactions on noradrenaline release in rabbit brain cortex. Naunyn-Schmiedeberg's Arch Pharmacol 338:53–61

    Google Scholar 

  • Lord JAH, Waterfield AA, Hughes J, Kosterlitz HW (1977) Endogenous opioid peptides: multiple agonists and receptors. Nature 267:495–499

    Google Scholar 

  • Loughlin SE, Fallon JH (1985) Locus coeruleus. In: Paxinos G (ed) The rat nervous system, vol 2, Hindbrain and spinal cord. Academic Press, Sydney, pp 79–93

    Google Scholar 

  • Marwaha J, Aghajanian GK (1982) Relative potencies of α1- and α2-antagonists in the locus ceruleus, dorsal raphe and dorsal lateral geniculate nuclei: an electrophysiological study. J Pharmacol Exp Ther 222:287–293

    Google Scholar 

  • North RA (1986) Receptors on individual neurones. Neuroscience 17:899–907

    Google Scholar 

  • North RA, Williams JT (1985) On the potassium conductance increased by opioids in rat locus coeruleus neurones. J Physiol 364:265–280

    Google Scholar 

  • North RA, Williams JT, Surprenant A, Christie MJ (1987) μ and δ receptors belong to a family of receptors that are coupled to potassium channels. Proc Natl Acad Sci USA 84:5487–5491

    Google Scholar 

  • Paterson SJ, Robson LE, Kosterlitz HW (1983) Classification of opioid receptors. Br Med Bull 39:31–36

    Google Scholar 

  • Ramme D, Illes P, Späth L, Starke K (1986) Blockade of α2-adrenoceptors permits the operation of otherwise silent opioid κ-receptors at the sympathetic axons of rabbit jejunal arteries. Naunyn-Schmiedeberg's Arch Pharmacol 334:48–55

    Google Scholar 

  • Regenold JT, Haas HL, Illes P (1988) Effects of purinoceptor agonists on electrophysiological properties of rat mesencephalic trigeminal neurones in vitro. Neurosci Lett 92:347–350

    Google Scholar 

  • Schoffelmeer ANM, Putters J, Mulder AH (1986) Activation of presynaptic α2-adrenoceptors attenuates the inhibitory effect of μ-opioid receptor agonists on noradrenaline release from brain slices. Naunyn-Schmiedeberg's Arch Pharmacol 333:377–380

    Google Scholar 

  • Snedecor GW, Cochran WG (1980) Statistical methods. Iowa State University Press, Ames

    Google Scholar 

  • Starke K (1977) Regulation of noradrenaline release by presynaptic receptor systems. Rev Physiol Biochem Pharmacol 7:1–124

    Google Scholar 

  • Surprenant A, Williams JT (1987) Inhibitory synaptic potentials recorded from mammalian neurones prolonged by blockade of noradrenaline uptake. J Physiol 382:87–103

    Google Scholar 

  • Weitzell R, Tanaka T, Starke K (1979) Pre- and postsynaptic effects of yohimbine stereoisomers on noradrenaline transmission in the pulmonary artery of the rabbit. Naunyn-Schmiedeberg's Arch Pharmacol 308:127–136

    Google Scholar 

  • Werling LL, McMahon PN, Cox BM (1989) Effects of pertussis toxin on opioid regulation of catecholamine release from rat and guinea pig brain slices. Naunyn-Schmiedeberg's Arch Pharmacol 339:509–513

    Google Scholar 

  • Williams JT, North RA (1984) Opiate-receptor interactions on single locus coeruleus neurones. Mol Pharmacol 26:489–497

    Google Scholar 

  • Williams JT, Egan TM, North RA (1982) Enkephalin opens potassium channels on mammalian central neurones. Nature 229:74–77

    Google Scholar 

  • Williams JT, Henderson G, North RA (1985) Characterization of α2-adrenoceptors which increase potassium conductance in rat locus coeruleus neurones. Neuroscience 14:95–101

    Google Scholar 

  • Williams JT, North RA, Tokimasa T (1988) Inward rectification of resting and opiate-activated potassium currents in rat locus coeruleus neurons. J Neurosci 8:4299–4306

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of Freiburg, Hermann-Herder-Strasse 5, W-7800, Freiburg, Federal Republic of Germany

    Peter Illes & Wolfgang Nörenberg

Authors
  1. Peter Illes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wolfgang Nörenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Send offprint requests to: P. Illes at the above address

Rights and permissions

Reprints and permissions

About this article

Cite this article

Illes, P., Nörenberg, W. Blockade of α2-adrenoceptors increases opioid μ-receptor-mediated inhibition of the firing rate of rat locus coeruleus neurones. Naunyn-Schmiedeberg's Arch Pharmacol 342, 490–496 (1990). https://doi.org/10.1007/BF00169034

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00169034

Key words

Search

Navigation