Wallukat Gerd, Mattecka Stephan, Wenzel Katrin, Schrödl Wieland, Vogt Birgit, Brunner Patrizia, Sheriff Ahmed, Kunze Rudolf
Berlin Cures GmbH, BBB Campus, 13125 Berlin, Germany.
Pentracor GmbH, 16761 Hennigsdorf, Germany.
J Clin Med. 2022 Feb 17;11(4):1058. doi: 10.3390/jcm11041058.
Recently, C-reactive protein (CRP) was shown to affect intracellular calcium signaling and blood pressure in vitro and in vivo, respectively. The aim of the present study was to further investigate if a direct effect on G-protein coupled receptor (GPCR) signaling by CRP can be observed by using CRP in combination with different GPCR agonists on spontaneously beating cultured neonatal rat cardiomyocytes. All used agonists (isoprenaline, clenbuterol, phenylephrine, angiotensin II and endothelin 1) affected the beat rate of cardiomyocytes significantly and after washing them out and re-stimulation the cells developed a pronounced desensitization of the corresponding receptors. CRP did not affect the basal beating-rate nor the initial increase/decrease in beat-rate triggered by different agonists. However, CRP co-incubated cells did not exhibit desensitization of the respective GPCRs after the stimulation with the different agonists. This lack of desensitization was independent of the GPCR type, but it was dependent on the CRP concentration. Therefore, CRP interferes with the desensitization of GPCRs and has to be considered as a novel regulator of adrenergic, angiotensin-1 and endothelin receptors.
最近，研究表明C反应蛋白（CRP）分别在体外和体内影响细胞内钙信号传导和血压。本研究的目的是通过将CRP与不同的G蛋白偶联受体（GPCR）激动剂联合应用于自发搏动的培养新生大鼠心肌细胞，进一步研究是否能观察到CRP对GPCR信号传导的直接影响。所有使用的激动剂（异丙肾上腺素、克伦特罗、去氧肾上腺素、血管紧张素II和内皮素1）均显著影响心肌细胞的搏动频率，在将它们洗脱并重新刺激后，细胞对相应受体产生明显的脱敏作用。CRP既不影响基础搏动频率，也不影响不同激动剂引发的搏动频率的初始增加/降低。然而，用不同激动剂刺激后，与CRP共同孵育的细胞并未表现出相应GPCR的脱敏现象。这种脱敏缺失与GPCR类型无关，但依赖于CRP浓度。因此，CRP干扰GPCR的脱敏过程，必须被视为肾上腺素能、血管紧张素-1和内皮素受体的新型调节剂。
