{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T04:56:03Z","timestamp":1794027363351,"version":"4.8.0"},"reference-count":63,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/F\/20\/110007"],"award-info":[{"award-number":["RG\/F\/20\/110007"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,7,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The endothelium's control of nearly all vascular function relies on rapid intercellular communication to coordinate cellular activity across scale. A key form of intercellular communication arises from the regenerative propagation of IP\n                    <jats:sub>3<\/jats:sub>\n                    \u2010evoked Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signals from cell to cell, which regulate vessel tone, modulate vascular permeability, and determine immune responses. Despite their importance, the mechanisms by which regenerative propagation of IP\n                    <jats:sub>3<\/jats:sub>\n                    \u2010evoked Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signals occurs are poorly understood. Here, in intact resistance arteries, precision photolysis of IP\n                    <jats:sub>3<\/jats:sub>\n                    combined with high\u2010resolution mesoscale imaging, targeted drug application, and advanced analytical techniques was used to determine the mechanisms underlying regenerative propagation of IP\n                    <jats:sub>3<\/jats:sub>\n                    \u2010evoked Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signals in the endothelium. Elevated IP\n                    <jats:sub>3<\/jats:sub>\n                    in the initiating cell triggers a noncanonical inside\u2010out signaling mechanism that leads to transcellular activation of a G\n                    <jats:sub>\u03b1q\/11<\/jats:sub>\n                    \u2010coupled receptor in a neighboring (receiving) cell. This, in turn, initiates canonical outside\u2010in signaling via PLC, leading to the hydrolysis of PIP\n                    <jats:sub>2<\/jats:sub>\n                    and production of IP\n                    <jats:sub>3<\/jats:sub>\n                    . This process creates a regenerative, IP\n                    <jats:sub>3<\/jats:sub>\n                    \u2010dependent signaling cascade operating between adjacent cells. Notably, neither Ca\n                    <jats:sup>2+<\/jats:sup>\n                    nor IP\n                    <jats:sub>3<\/jats:sub>\n                    diffusion through gap junctions plays a significant role in intercellular communication. Our findings uncover a previously unrecognized mechanism of endothelial communication, in which noncanonical IP\n                    <jats:sub>3<\/jats:sub>\n                    \u2010driven transcellular activation of G protein\u2010coupled receptors sustains a regenerative signaling loop, highlighting a novel framework for intercellular coordination in the vascular endothelium.\n                  <\/jats:p>","DOI":"10.1096\/fj.202500370rr","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T11:39:36Z","timestamp":1752147576000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Inside\u2010Out\n                    <scp>IP<\/scp>\n                    <sub>3<\/sub>\n                    \u2010Mediated G Protein\u2010Coupled Receptor Activation Drives Intercellular Ca\n                    <sup>2+<\/sup>\n                    Signaling in the Vascular Endothelium"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7961-4544","authenticated-orcid":false,"given":"C.","family":"Buckley","sequence":"first","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences University of Strathclyde  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0790-4291","authenticated-orcid":false,"given":"X.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences University of Strathclyde  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8265-382X","authenticated-orcid":false,"given":"M. D.","family":"Lee","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences University of Strathclyde  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2500-0632","authenticated-orcid":false,"given":"C.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences University of Strathclyde  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3302-3984","authenticated-orcid":false,"given":"J. 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