{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T04:23:57Z","timestamp":1771561437840,"version":"3.50.1"},"reference-count":27,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2010,2]]},"abstract":"<jats:p> Adenosine has been shown to exert direct antihypertrophic effects on the heart, and plasma adenosine levels have been shown to be elevated in patients with heart failure. It has therefore been proposed that endogenously synthesized adenosine may function as a cardiac antihypertrophic factor. The present study was aimed to determine whether the adenosine system is altered in a potential adaptive manner following phenylephrine-induced hypertrophy in cultured neonatal rat ventricular myocytes. Phenylephrine produced significant hypertrophy as determined by cell size and atrial natriuretic peptide gene expression, which was accompanied by significantly increased gene and protein expression of adenosine A<jats:sub>1<\/jats:sub>, A<jats:sub>2a<\/jats:sub>, and A<jats:sub>3<\/jats:sub> receptors. These effects and the hypertrophic response were prevented by the \u03b1<jats:sub>1<\/jats:sub>-adrenoceptor antagonist prazosin as well as pharmacological agonists for all adenosine receptor subtypes. The upregulation of adenosine receptors by phenylephrine was also abrogated by adenosine 5\u2032-(\u03b1,\u03b2-methylene)diphosphate, an inhibitor of ectosolic 5\u2032-nucleotidase. Moreover, phenylephrine significantly increased production of adenosine from myocytes in the presence of a nucleoside transport and adenosine deaminase inhibitor, the combination of which abrogated the hypertrophic effect of phenylephrine. The latter effect was reversed by adenosine receptor antagonists. Phenylephrine also produced a significant upregulation in expression levels of equilibrative nucleoside transporter 1 although expression levels of equilibrative nucleoside transporter 2 were unaffected. Taken together, our results suggest an adaptive upregulation of the adenosine system to phenylephrine-induced cardiomyocyte hypertrophy that serves to limit the hypertrophic effect of \u03b1<jats:sub>1-<\/jats:sub>adrenoceptor activation. <\/jats:p>","DOI":"10.1152\/ajpheart.00417.2009","type":"journal-article","created":{"date-parts":[[2009,12,4]],"date-time":"2009-12-04T22:19:45Z","timestamp":1259965185000},"page":"H545-H553","source":"Crossref","is-referenced-by-count":16,"title":["Compensatory upregulation of the adenosine system following phenylephrine-induced hypertrophy in cultured rat ventricular myocytes"],"prefix":"10.1152","volume":"298","author":[{"given":"Theresa","family":"Pang","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong Tracey","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Freeman","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, and"},{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Western Ontario, London, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morris","family":"Karmazyn","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0531-5565(03)00095-0"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2003.10.127"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2003.11.031"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s002100000318"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.15.2041"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.65.092101.142243"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000120390.68287.BB"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.95.6.1363"},{"key":"B9","doi-asserted-by":"crossref","unstructured":"Gan XT, Rajapurohitam V, Haist JV, Chidiac P, Cook MA,  Karmazyn M. 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