Co-incident signalling between μ-opioid and M3 muscarinic receptors at the level of Ca2 release from intracellular stores: Lack of evidence for Ins(1,4,5)P3 receptor sensitization

Abstract

Activation of Gi/Go-coupled opioid receptors increases [Ca2+]i (intracellular free-Ca2+ concentration), but only if there is concomitant Gq-coupled receptor activation. This Gi/Go-coupled receptor-mediated [Ca 2+]i increase does not appear to result from further production of InsP3 [Ins(1,4,5)P3] in SH-SY5Y cells. In the present study, fast-scanning confocal microscopy revealed that activation of μ-opioid receptors alone by 1 μM DAMGO ([D-Ala, NMe-Phe, Gly-ol]-enkephalin) did not stimulate the InsP3-dependent elementary Ca2+-signalling events (Ca2+ puffs), whereas DAMGO did evoke Ca2+ puffs when applied during concomitant activation of M 3 muscarinic receptors with 1 μM carbachol. We next de..