{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T20:44:59Z","timestamp":1770151499896,"version":"3.49.0"},"reference-count":58,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2008,1]]},"abstract":"<jats:p>Although \u03b2<jats:sub>2<\/jats:sub>-adrenoceptors represent 15\u201325% of \u03b2-adrenoceptors in the guinea pig heart, their functionality is controversial. We assessed the inotropic effects of \u03b2<jats:sub>2<\/jats:sub>-adrenoceptor partial agonists in right papillary muscles. Salbutamol induced a small but significant concentration-dependent negative inotropic effect (NIE, \u22125% at 60 nM) followed by a moderate positive inotropic effect (+36% at 6 \u03bcM) due to activation of \u03b2<jats:sub>1<\/jats:sub>-adrenoceptors. In the presence of 4 \u03bcM atenolol, the concentration-dependent NIE (\u221212% at 6 \u03bcM) was biphasic, best described by a double logistic equation with respective EC<jats:sub>50<\/jats:sub>values of 3 and \u223c420 nM, and was insensitive to SR59230A. In muscles from pertussis toxin-treated guinea pigs, the salbutamol-induced positive inotropic effect was sensitive to low concentrations of ICI-118551 in an unusual manner. Experiments in reserpinized animals revealed the importance of the phosphorylation-dephosphorylation processes. PKA inhibition reduced and suppressed the effects obtained at low and high concentrations, respectively, indicating that its activation was a prerequisite to the NIE. The effect occurring at nanomolar concentrations depended upon PKA\/phosphatidylinositol 3-kinase\/cytosolic phospholipase A<jats:sub>2<\/jats:sub>(cPLA<jats:sub>2<\/jats:sub>) activations leading to nitric oxide (NO) release via the arachidonic acid\/cyclooxygenase pathway. NO release via PKA-dependent phosphorylation of the receptor was responsible for the inotropic effect observed at submicromolar concentrations, which is negatively controlled by cPLA<jats:sub>2<\/jats:sub>. The possibility that these effects are due to an equilibrium between different affinity states of the receptor (G<jats:sub>s<\/jats:sub>\/G<jats:sub>i<\/jats:sub>coupled and G<jats:sub>i<\/jats:sub>independent with different signaling pathways) that can be displaced by ICI-118551 is discussed. We conclude that \u03b2<jats:sub>2<\/jats:sub>-adrenoceptors are functional in guinea pig heart and can modulate the inotropic state.<\/jats:p>","DOI":"10.1152\/ajpcell.00231.2007","type":"journal-article","created":{"date-parts":[[2007,10,18]],"date-time":"2007-10-18T01:24:57Z","timestamp":1192670697000},"page":"C106-C117","source":"Crossref","is-referenced-by-count":6,"title":["Roles of PKA, PI3K, and cPLA<sub>2<\/sub>in the NO-mediated negative inotropic effect of \u03b2<sub>2<\/sub>-adrenoceptor agonists in guinea pig right papillary muscles"],"prefix":"10.1152","volume":"294","author":[{"given":"Fabien A.","family":"Faucher","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7ois E.","family":"Gannier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques M.","family":"Lignon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Cosnay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire O.","family":"Mal\u00e9cot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"A\u00eft-Mamar B, Cailleret M, R\u00fccker-Martin C, Bouabdallah A, Candiani G, Adamy C, Duvaldestin P, Pecker F, Defer N, Pavoine C.The cytosolic phospholipase A2pathway, a safeguard of \u03b22-adrenergic cardiac effects in rat.J Biol Chem280: 18881\u201318890, 2005.","DOI":"10.1074\/jbc.M410305200"},{"key":"R2","unstructured":"Ariens EJ, Van Rossum JM.pDx, pAx and pDx values in the analysis of pharmacodynamics.Arch Int Pharmacodyn110: 275\u2013299, 1957."},{"key":"R3","doi-asserted-by":"crossref","unstructured":"Balijepalli RC, Foell JD, Hall DD, Hell JW, Kamp TJ.Localization of cardiac L-type Ca2+channels to a caveolar macromolecular signaling complex is required for \u03b22-adrenergic regulation.Proc Natl Acad Sci USA103: 7500\u20137505, 2006.","DOI":"10.1073\/pnas.0503465103"},{"key":"R4","doi-asserted-by":"crossref","unstructured":"Balligand JL, Cannon PJ.Nitric oxide synthases and cardiac muscle. 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