RT Journal Article SR Electronic T1 δ-Opioid-Induced Liberation of Gβγ Mobilizes Ca2+ Stores in NG108-15 Cells JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 902 OP 908 DO 10.1124/mol.56.5.902 VO 56 IS 5 A1 Shin Hee Yoon A1 Tak-Man Lo A1 Horace H. Loh A1 Stanley A. Thayer YR 1999 UL http://molpharm.aspetjournals.org/content/56/5/902.abstract AB Activation of δ-opioid receptors in NG108-15 cells releases Ca2+ from an intracellular store through activation of a pertussis toxin-sensitive G protein. We tested the hypothesis that activation of δ-opioid receptors mobilizes inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+stores via liberation of Gβγ. Fura-2-based digital imaging was used to study the mechanism of opioid-induced increases in [Ca2+]i in NG108-15 cells. Exposure tod-Ala2-d-Leu5enkephalin (100 nM) for 90 s induced increases in [Ca2+]i that were blocked by microinjection of the IP3 receptor antagonist heparin (pipette concentration = 100 mg/ml) but not by sham injection. Microinjection of a peptide that binds Gβγ (QEHA, 1 mM) decreased the d-Ala2-d-Leu5enkephalin-evoked response. Microinjection of an inactive peptide (SKEE, 1 mM) that does not bind to Gβγ failed to inhibit the opioid-induced increase in [Ca2+]i. Microinjection of a peptide (QLKK, 15 mM) that binds to free Gαq blocked the increase evoked by 3 nM bradykinin, but microinjection of an inactive peptide (ADRK, 15 mM) did not. Microinjection of QLKK did not significantly affect the opioid-induced increase in [Ca2+]i. Collectively, these data demonstrate that activation of δ-opioid receptors induces the release of Ca2+ from IP3-sensitive stores in NG108-15 cells through activation of the βγ subunits of inhibitory G proteins.