Jankowski M, Hajjar F, Kawas S A, Mukaddam-Daher S, Hoffman G, McCann S M, Gutkowska J
Centre de Recherche, Centre Hospitalier de l'Université de Montréal, Campus Hôtel-Dieu, Montreal, H2W 1T8 Canada.
Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14558-63. doi: 10.1073/pnas.95.24.14558.
We report here that the rat heart is a site of oxytocin (OT) synthesis and release. Oxytocin was detected in all four chambers of the heart. The highest OT concentration was in the right atrium (2128 +/- 114 pg/mg protein), which was 19-fold higher than in rat uterus but 3.3-fold lower than in the hypothalamus. OT concentrations were significantly greater in the right and left atria than in the corresponding ventricles. Furthermore, OT was released into the effluent of isolated, perfused rat heart (34.5 +/- 4.7 pg/min) and into the medium of cultured atrial myocytes. Reverse-phase HPLC purification of the heart extracts and heart perfusates revealed a main peak identical with the retention time of synthetic OT. Southern blots of reverse transcription-PCR products from rat heart revealed gene expression of specific OT mRNA. OT immunostaining likewise was found in atrial myocytes and fibroblasts, and the intensity of positive stains from OT receptors paralleled the atrial natriuretic peptide stores. Our findings suggest that heart OT is structurally identical, and therefore derived from, the same gene as the OT that is primarily found in the hypothalamus. Thus, the heart synthesizes and processes a biologically active form of OT. The presence of OT and OT receptor in all of the heart's chambers suggests an autocrine and/or paracrine role for the peptide. Our finding of abundant OT receptor in atrial myocytes supports our hypothesis that OT, directly and/or via atrial natriuretic peptide release, can regulate the force of cardiac contraction.
我们在此报告，大鼠心脏是催产素（OT）合成与释放的场所。在心脏的所有四个腔室中均检测到催产素。催产素浓度最高的是右心房（2128±114 pg/mg蛋白质），比大鼠子宫中的浓度高19倍，但比下丘脑低3.3倍。右心房和左心房中的催产素浓度显著高于相应的心室。此外，催产素释放到离体灌注大鼠心脏的流出液中（34.5±4.7 pg/分钟）以及培养的心房肌细胞的培养基中。对心脏提取物和心脏灌注液进行反相高效液相色谱纯化后，发现一个主峰，其保留时间与合成催产素相同。对大鼠心脏逆转录-聚合酶链反应产物进行Southern印迹分析，显示出特定催产素mRNA的基因表达。在心房肌细胞和成纤维细胞中也发现了催产素免疫染色，催产素受体阳性染色的强度与心房利钠肽的储存量平行。我们的研究结果表明，心脏催产素在结构上与主要在下丘脑中发现的催产素相同，因此来源于同一基因。因此，心脏合成并加工出一种具有生物活性的催产素形式。心脏所有腔室中都存在催产素和催产素受体，这表明该肽具有自分泌和/或旁分泌作用。我们在心房肌细胞中发现大量催产素受体，这支持了我们的假设，即催产素可直接和/或通过心房利钠肽的释放来调节心脏收缩力。
