{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T16:12:17Z","timestamp":1773418337652,"version":"3.50.1"},"reference-count":61,"publisher":"Society for Neuroscience","issue":"10","license":[{"start":{"date-parts":[[2014,9,5]],"date-time":"2014-09-05T00:00:00Z","timestamp":1409875200000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2014,3,5]]},"abstract":"<jats:p>\u03bc-Opioid agonists have no effect on calcium currents (<jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub>) in neurohypophysial terminals when recorded using the classic whole-cell patch-clamp configuration. However, \u03bc-opioid receptor (MOR)-mediated inhibition of<jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub>is reliably demonstrated using the perforated-patch configuration. This suggests that the MOR-signaling pathway is sensitive to intraterminal dialysis and is therefore mediated by a readily diffusible second messenger. Using the perforated patch-clamp technique and ratio-calcium-imaging methods, we describe a diffusible second messenger pathway stimulated by the MOR that inhibits voltage-gated calcium channels in isolated terminals from the rat neurohypophysis (NH). Our results show a rise in basal intracellular calcium ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) in response to application of [<jats:sc>d<\/jats:sc>-Ala<jats:sup>2<\/jats:sup>-N-Me-Phe<jats:sup>4<\/jats:sup>,Gly5-ol]-Enkephalin (DAMGO), a MOR agonist, that is blocked by<jats:sc>d<\/jats:sc>-Phe-Cys-Tyr-<jats:sc>d<\/jats:sc>-Trp-Orn-Thr-Pen-Thr-NH<jats:sub>2<\/jats:sub>(CTOP), a MOR antagonist. Buffering DAMGO-induced changes in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>with BAPTA-AM completely blocked the inhibition of both<jats:italic>I<\/jats:italic><jats:sub><jats:italic>Ca<\/jats:italic><\/jats:sub>and high-K<jats:sup>+<\/jats:sup>-induced rises in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>due to MOR activation, but had no effect on \u03ba-opioid receptor (KOR)-mediated inhibition. Given the presence of ryanodine-sensitive stores in isolated terminals, we tested 8-bromo-cyclic adenosine diphosphate ribose (8Br-cADPr), a competitive inhibitor of cyclic ADP-ribose (cADPr) signaling that partially relieves DAMGO inhibition of<jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub>and completely relieves MOR-mediated inhibition of high-K<jats:sup>+<\/jats:sup>-induced and DAMGO-induced rises in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. Furthermore, antagonist concentrations of ryanodine completely blocked MOR-induced increases in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>and inhibition of<jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub>and high-K<jats:sup>+<\/jats:sup>-induced rises in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>while not affecting KOR-mediated inhibition. Antagonist concentrations of ryanodine also blocked MOR-mediated inhibition of electrically-evoked increases in capacitance. These results strongly suggest that a key diffusible second messenger mediating the MOR-signaling pathway in NH terminals is [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>released by cADPr from ryanodine-sensitive stores.<\/jats:p>","DOI":"10.1523\/jneurosci.2505-13.2014","type":"journal-article","created":{"date-parts":[[2014,3,5]],"date-time":"2014-03-05T17:36:35Z","timestamp":1394040995000},"page":"3733-3742","source":"Crossref","is-referenced-by-count":17,"title":["\u03bc-Opioid Inhibition of Ca<sup>2+<\/sup>Currents and Secretion in Isolated Terminals of the Neurohypophysis Occurs via Ryanodine-Sensitive Ca<sup>2+<\/sup>Stores"],"prefix":"10.1523","volume":"34","author":[{"given":"Cristina","family":"Vel\u00e1zquez-Marrero","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Ortiz-Miranda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9ctor 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