{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:46:37Z","timestamp":1791326797937,"version":"4.3.1"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2001,8,31]]},"abstract":"<jats:p>\n            The gut hormone, glucagon-like peptide-1 (GLP-1), which is secreted in nanomolar amounts in response to nutrients in the intestinal lumen, exerts cAMP\/protein kinase A\u2013mediated insulinotropic actions in target endocrine tissues, but its actions in heart cells are unknown. GLP-1 (10 nmol\/L) increased intracellular cAMP (from 5.7\u00b10.5 to 13.1\u00b10.12 pmol\/mg protein) in rat cardiac myocytes. The effects of cAMP-doubling concentrations of both GLP-1 and isoproterenol (ISO, 10 nmol\/L) on contraction amplitude, intracellular Ca\n            <jats:sup>2+<\/jats:sup>\n            transient (CaT), and pH\n            <jats:sub>i<\/jats:sub>\n            in indo-1 and seminaphthorhodafluor (SNARF)\u20131 loaded myocytes were compared. Whereas ISO caused a characteristic increase (above baseline) in contraction amplitude (160\u00b134%) and CaT (70\u00b15%), GLP-1 induced a significant decrease in contraction amplitude (\u221227\u00b15%) with no change in the CaT after 20 minutes. Neither pertussis toxin treatment nor exposure to the cGMP-stimulated phosphodiesterase (PDE2) inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine or the nonselective PDE inhibitor 3-isobutyl-1-methylxanthine nor the phosphatase inhibitors okadaic acid or calyculin A unmasked an ISO-mimicking response of GLP-1. In SNARF-1\u2013loaded myocytes, however, both ISO and GLP-1 caused an intracellular acidosis (\u0394pH\n            <jats:sub>i<\/jats:sub>\n            \u22120.09\u00b10.02 and \u22120.08\u00b10.03, respectively). The specific GLP-1 antagonist exendin 9-39 and the cAMP inhibitory analog Rp-8CPT-cAMPS inhibited both the GLP-1\u2013induced intracellular acidosis and the negative contractile effect. We conclude that in contrast to \u03b2-adrenergic signaling, GLP-1 increases cAMP but fails to augment contraction, suggesting the existence of functionally distinct adenylyl cyclase\/cAMP\/protein kinase A compartments, possibly determined by unique receptor signaling microdomains that are not controlled by pertussis toxin\u2013sensitive G proteins or by enhanced local PDE or phosphatase activation. Furthermore, GLP-1 elicits a cAMP-dependent modest negative inotropic effect produced by a decrease in myofilament-Ca\n            <jats:sup>2+<\/jats:sup>\n            responsiveness probably resulting from intracellular acidification.\n          <\/jats:p>","DOI":"10.1161\/hh1701.095716","type":"journal-article","created":{"date-parts":[[2007,9,28]],"date-time":"2007-09-28T18:32:49Z","timestamp":1191004369000},"page":"445-452","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":141,"title":["Glucagon-Like Peptide-1 Increases cAMP but Fails to Augment Contraction in Adult Rat Cardiac Myocytes"],"prefix":"10.1161","volume":"89","author":[{"given":"Marti\u0301n G.","family":"Vila Petroff","sequence":"first","affiliation":[{"name":"From the Laboratory of Cardiovascular Sciences (S.J.S.) and Diabetes Section (J.M.E., X.W.), Gerontology Research Center, Intramural Research Program, National Institute on Aging, NIH, Baltimore, Md, and Centro de Investigaciones Cardiovasculares (M.G.V.P.), Facultad de Ciencias Me\u0301dicas, Universidad Nacional de La Plata, La Plata, Argentina."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine M.","family":"Egan","sequence":"additional","affiliation":[{"name":"From the Laboratory of Cardiovascular Sciences (S.J.S.) and Diabetes Section (J.M.E., X.W.), Gerontology Research Center, Intramural Research Program, National Institute on Aging, NIH, Baltimore, Md, and Centro de Investigaciones Cardiovasculares (M.G.V.P.), Facultad de Ciencias Me\u0301dicas, Universidad Nacional de La Plata, La Plata, Argentina."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Laboratory of Cardiovascular Sciences (S.J.S.) and Diabetes Section (J.M.E., X.W.), Gerontology Research Center, Intramural Research Program, National Institute on Aging, NIH, Baltimore, Md, and Centro de Investigaciones Cardiovasculares (M.G.V.P.), Facultad de Ciencias Me\u0301dicas, Universidad Nacional de La Plata, La Plata, Argentina."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Sollott","sequence":"additional","affiliation":[{"name":"From the Laboratory of Cardiovascular Sciences (S.J.S.) and Diabetes Section (J.M.E., X.W.), Gerontology Research Center, Intramural Research Program, National Institute on Aging, NIH, Baltimore, Md, and Centro de Investigaciones Cardiovasculares (M.G.V.P.), Facultad de Ciencias Me\u0301dicas, Universidad Nacional de La Plata, La Plata, Argentina."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9136(199602)13:2<156::AID-DIA59>3.0.CO;2-U"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)01430-9"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.132.1.8380389"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00400823"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.30.17749"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2460687"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)33279-4"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.92.4.509"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.88.5.589"},{"key":"e_1_3_3_10_2","first-page":"574","volume":"258","year":"1990","unstructured":"Spurgeon HA, Stern MD, Baartz G, Raffaeli S, Hansford RG, Talo A, Lakatta EG, Capogrossi MG. 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