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

Damlen S K Samways, Wen Hong Li, Stuart J. Conway, Andrew B. Holmes, Martin D. Bootman, Graeme Henderson

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 determined whether μ-opioid receptor activation might increase [Ca2+] i by sensitizing the InsP3 receptor to InsP3. DAMGO did not potentiate the amplitude of the [Ca2+]i increase evoked by flash photolysis of the caged InsP3 receptor agonist, caged 2,3-isopropylidene-InsP3, whereas the InsP 3 receptor sensitizing agent, thimerosal (10 μM), did potentiate this response. DAMGO also did not prolong the rate of decay of the increase in [Ca2+]i evoked by flash photolysis of caged 2,3-isopropylidene-InsP3. Furthermore, DAMGO did not increase [Ca2+], in the presence of the cell-membrane-permeable InsP 3 receptor agonist, InsP3 hexakis(butyryloxymethyl) ester. Therefore it appears that μ-opioid receptors do not increase [Ca 2+]i through either InsP3 receptor sensitization, enhancing the releasable pool of Ca2+ or inhibition of Ca2+ removal from the cytoplasm.

Original languageEnglish (US)
Pages (from-to)713-720
Number of pages8
JournalBiochemical Journal
Volume375
Issue number3
DOIs
StatePublished - Nov 1 2003

Fingerprint

Muscarinic M3 Receptors
Ala(2)-MePhe(4)-Gly(5)-enkephalin
Opioid Analgesics
Opioid Receptors
Chemical activation
Photolysis
Thimerosal
Inositol 1,4,5-Trisphosphate
Enkephalins
Confocal microscopy
Carbachol
Muscarinic Receptors
Cell membranes
Confocal Microscopy
Cytoplasm
Esters
Cell Membrane
Scanning

Keywords

  • μ-opioid
  • Ca
  • G-protein
  • InsP

ASJC Scopus subject areas

  • Biochemistry

Cite this

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. / Samways, Damlen S K; Li, Wen Hong; Conway, Stuart J.; Holmes, Andrew B.; Bootman, Martin D.; Henderson, Graeme.

In: Biochemical Journal, Vol. 375, No. 3, 01.11.2003, p. 713-720.

Research output: Contribution to journalArticle

Samways, Damlen S K ; Li, Wen Hong ; Conway, Stuart J. ; Holmes, Andrew B. ; Bootman, Martin D. ; Henderson, Graeme. / 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. In: Biochemical Journal. 2003 ; Vol. 375, No. 3. pp. 713-720.
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