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

Abstract

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. 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‐Pen^2,5]‐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. The GABA_B agonist baclofen inhibited I_Ba in all neurons (pEC₅₀ 5.9, maximum inhibition 42%). 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. A maximally effective concentration of endomorphin‐1 (30 μM) partially (19%), but significantly (PBa normally elicited by a maximally effective concentration of met‐enkephalin (10 μM). 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. British Journal of Pharmacology (1999) 126, 1553–1558; doi:10.1038/sj.bjp.0702457