Anand-Srivastava M B, Thibault G, Sola C, Fon E, Ballak M, Charbonneau C, Haile-Meskel H, Garcia R, Genest J, Cantin M
Department of Pathology, Université de Montréal, Quebec, Canada.
Hypertension. 1989 Jun;13(6 Pt 2):789-98. doi: 10.1161/01.hyp.13.6.789.
The Purkinje fibers of the rabbit false tendons (chordae tendineae spuriae) are endocrine cells containing immunoreactive atrial natriuretic factor (ANF) and ANF messenger RNA (mRNA). These cells, as visualized by immunocryoultramicrotomy, contain immunoreactive ANF in their secretory granules and their Golgi complex and exhibit ANF mRNA, as visualized by in situ hybridization with an ANF complementary RNA probe. The content of immunoreactive ANF and ANF mRNA of the Purkinje fibers is midway between that of atrial and ventricular working cardiocytes. High-pressure liquid chromatography analysis of immunoreactive ANF using antibodies against the C-terminal and N-terminal moieties of the molecule indicates that part of immunoreactive ANF contained in Purkinje fibers is the propeptide [Asn1,Tyr126]ANF whereas part was nonspecifically cleaved into C-terminal and N-terminal ANF. The chordae tendineae spuriae exhibit binding sites for ANF (Kd:approximately 1.0 nM; Bmax:approximately 2.3 fmol/mg). ANF profoundly decreases basal and stimulated (epinephrine, dopamine, isoproterenol, and forskolin) adenylate cyclase activity and cyclic adenosine monophosphate (AMP) levels. ANF has little effect on norepinephrine-stimulated adenylate cyclase activity or on norepinephrine-stimulated cyclic AMP levels. ANF produces only a slight increase in guanylate cyclase activity and cyclic guanosine monophosphate levels at high (10(7)-10(6) M) concentrations. These results suggest an autocrine function for ANF in the modulation of the impulse in the peripheral conduction cells (Purkinje fibers) of the rabbit through changes in second messenger levels.
兔假腱索(腱索)的浦肯野纤维是含有免疫反应性心房钠尿肽(ANF)和ANF信使核糖核酸(mRNA)的内分泌细胞。通过免疫冷冻超薄切片观察,这些细胞的分泌颗粒和高尔基体复合物中含有免疫反应性ANF,并且通过与ANF互补RNA探针进行原位杂交观察,显示出ANF mRNA。浦肯野纤维中免疫反应性ANF和ANF mRNA的含量介于心房和心室工作心肌细胞之间。使用针对该分子C末端和N末端部分的抗体对免疫反应性ANF进行高压液相色谱分析表明,浦肯野纤维中所含的部分免疫反应性ANF是前体肽[Asn1,Tyr126]ANF,而部分则非特异性地裂解为C末端和N末端ANF。腱索显示出ANF的结合位点(解离常数:约1.0 nM;最大结合容量:约2.3 fmol/mg)。ANF可显著降低基础和刺激(肾上腺素、多巴胺、异丙肾上腺素和福斯可林)状态下的腺苷酸环化酶活性和环磷酸腺苷(AMP)水平。ANF对去甲肾上腺素刺激的腺苷酸环化酶活性或去甲肾上腺素刺激的环AMP水平几乎没有影响。在高浓度(10⁷ - 10⁶ M)时,ANF仅使鸟苷酸环化酶活性和环磷酸鸟苷水平略有增加。这些结果表明,ANF在兔外周传导细胞(浦肯野纤维)中通过改变第二信使水平,对冲动调节具有自分泌功能。