μ-opioid receptor modulation of calcium channel current in periaqueductal grey neurons from C57B16/J mice and mutant mice lacking MOR-1

Mark Connor*, Alwin Schuller, John E. Pintar, MacDonald J. Christie

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

Abstract

1. The actions of opioid receptor agonists on the calcium channel currents (I(Ba)) of acutely dissociated periaqueductal grey (PAG) neurons from C57B16/J mice and mutant mice lacking the first exon of the μ-opioid receptor (MOR-1) were examined using whole cell patch clamp techniques. These effects were compared with the GABA(B)-receptor agonist baclofen. 2. The endogenous opioid agonist methionine-enkephalin (met-enkephalin, pEC50 6.8, maximum inhibition 40%), the putative endogenous μ-opioid agonist endomorphin-1 (pEC50 6.2, maximum inhibition 35%) and the μ-opioid selective agonist DAMGO (Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol enkephalin, pEC50 6.9, maximum inhibition 40%) inhibited I(Ba) in 70% of mouse PAG neurons. The inhibition of I(Ba) by each agonist was completely prevented by the μ-receptor antagonist CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2). The δ-opioid receptor agonists DPDPE ([D-Pen2,5]-enkephalin, 1 μM) and deltorphin II (1 μM), and the κ-opioid receptor agonist U-69593 (1-10 μM), did not affect I(Ba) in any cell tested. 3. The GABA(B) agonist baclofen inhibited I(Ba) in all neurons (pEC50 5.9, maximum inhibition 42%). 4. In neurons from the MOR-1 deficient mice, the μ-opioid agonists met-enkephalin, DAMGO and endomorphin-1 did not inhibit I(Ba), whilst baclofen inhibited I(Ba) in a manner indistinguishable from wild type mice. 5. A maximally effective concentration of endomorphin-1 (30 μM) partially (19%), but significantly (P < 0.005), occluded the inhibition of I(Ba) normally elicited by a maximally effective concentration of met-enkephalin (10 μM). 6. This study indicates that μ-opioid receptors, but not δ- or κ-opioid receptors, modulate somatic calcium channel currents in mouse PAG neurons. The putative endogenous μ-agonist, endomorphin-1, was a partial agonist in mouse PAG neurons.

Original languageEnglish
Pages (from-to)1553-1558
Number of pages6
JournalBritish Journal of Pharmacology
Volume126
Issue number7
Publication statusPublished - 1999

Keywords

  • μ-opioid receptor
  • Baclofen
  • Calcium channels
  • Endomorphin-1
  • Gene knockout
  • Partial agonist
  • Periaqueductal grey

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