{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:50:07Z","timestamp":1767919807051,"version":"3.49.0"},"reference-count":36,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2017,7,12]],"date-time":"2017-07-12T00:00:00Z","timestamp":1499817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01 GM101928"],"award-info":[{"award-number":["R01 GM101928"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01 GM107094"],"award-info":[{"award-number":["R01 GM107094"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 GM101928"],"award-info":[{"award-number":["R01 GM101928"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 GM107094"],"award-info":[{"award-number":["R01 GM107094"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Previous studies indicate that prostaglandin EP<jats:sub>2<\/jats:sub> receptors selectively couple to AC2 in non\u2010lipid raft domains of airway smooth muscle (ASM) cells, where they regulate specific cAMP\u2010dependent responses. The goal of the present study was to identify the cellular microdomains where EP<jats:sub>2<\/jats:sub> receptors stimulate cAMP production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>FRET\u2010based cAMP biosensors were targeted to different subcellular locations of primary human ASM cells. The Epac2\u2010camps biosensor, which expresses throughout the cell, was used to measure bulk cytoplasmic responses. Epac2\u2010MyrPalm and Epac2\u2010CAAX were used to measure responses associated with lipid raft and non\u2010raft regions of the plasma membrane respectively. Epac2\u2010NLS was used to monitor responses at the nucleus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Activation of AC with forskolin or \u03b2<jats:sub>2<\/jats:sub>\u2010adrenoceptors with isoprenaline increased cAMP in all subcellular locations. Activation of EP<jats:sub>2<\/jats:sub> receptors with butaprost produced cAMP responses that were most readily detected by the non\u2010raft and nuclear sensors, but only weakly detected by the cytosolic sensor and not detected at all by the lipid raft sensor. Exposure to rolipram, a PDE4 inhibitor, unmasked the ability of EP<jats:sub>2<\/jats:sub> receptors to increase cAMP levels associated with lipid raft domains. Overexpression of AC2 selectively increased EP<jats:sub>2<\/jats:sub> receptor\u2010stimulated production of cAMP in non\u2010raft membrane domains.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>EP<jats:sub>2<\/jats:sub> receptor activation of AC2 leads to cAMP production in non\u2010raft and nuclear compartments of human ASMs, while \u03b2<jats:sub>2<\/jats:sub> adrenoceptor signalling is broadly detected across microdomains. The activity of PDE4 appears to play a role in maintaining the integrity of compartmentalized EP<jats:sub>2<\/jats:sub> receptor responses in these cells.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13904","type":"journal-article","created":{"date-parts":[[2017,6,12]],"date-time":"2017-06-12T03:46:41Z","timestamp":1497239201000},"page":"2784-2796","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Compartmentalized cAMP responses to prostaglandin EP<sub>2<\/sub> receptor activation in human airway smooth muscle cells"],"prefix":"10.1111","volume":"174","author":[{"given":"Shailesh R","family":"Agarwal","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of Nevada, Reno School of Medicine  Reno NV USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn","family":"Miyashiro","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Nevada, Reno School of Medicine  Reno NV USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Htun","family":"Latt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Nevada, Reno School of Medicine  Reno NV USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rennolds S","family":"Ostrom","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences Chapman University School of Pharmacy  Irvine CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8499-8765","authenticated-orcid":false,"given":"Robert D","family":"Harvey","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Nevada, Reno School of Medicine  Reno NV 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