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

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 mu-opioid receptor (MO R-1) were examined using whole cell patch clamp techniques. These effects w ere compared with the GABA(B)-receptor agonist baclofen. 2 The endogenous opioid agonist methionine-enkephalin (met-enkephalin, pEC( 50) 6.8, maximum inhibition 40%), the putative endogenous mu-opioid agonist endomorphin-1 (pEC(50) 6.2, maximum inhibition 35%) and the mu-opioid sele ctive agonist DAMGO (Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol enkephalin, pEC(50) 6.9, maximum inhibition 40%) inhibited I-Ba in 70% of mouse FAG neurons. The in hibition of I-Ba by each agonist was completely prevented by the mu-recepto r antagonist CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2). The delta-opio id receptor agonists DPDPE ([D-Pen(2,5)]-enkephalin, 1 mu M) and deltorphin II (1 mu M), and the kappa-opioid receptor agonist U-69593 (1-10 mu M), di d not affect I-Ba in any cell tested. 3 The GABA(B) agonist baclofen inhibited I-Ba in all neurons (pEC(50) 5.9, maximum inhibition 42%). 4 In neurons from the MOR-1 deficient mice, the mu-opioid agonists met-enke phalin, DAMGO and endomorphin-1 did not inhibit 4, whilst baclofen inhibite d I-Ba in a manner indistinguishable from wild type mice. 5 A maximally effective concentration of endomorphin-1 (30 mu M) partially (19%), but significantly (P<0.005), occluded the inhibition of I-Ba normall y elicited by a maximally effective concentration of met-enkephalin (10 mu M). 6 This study indicates that mu-opioid receptors, but not delta- or kappa-op ioid receptors, modulate somatic calcium channel currents in mouse FAG neur ons. The putative endogenous mu-agonist, endomorphin-1, was a partial agoni st in mouse FAG neurons.