Molecular signaling of G-protein-coupled receptor in chronic heart failure and associated complications |
| |
| Authors: | Mohammad Altamish Vijaya Paul Samuel Rajiv Dahiya Yogendra Singh Pran Kishore Deb Hamid A. Bakshi Murtaza M. Tambuwala Dinesh K. Chellappan Trudi Collet Kamal Dua Gaurav Gupta |
| |
| Affiliation: | 1. Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India;2. Department of Anatomy, RAK College of Medicine, RAK Medical and Health Sciences University, Ras Al Khaimah, UAE;3. Laboratory of Peptide Research and Development, School of Pharmacy, Faculty of Medical Sciences, The University of the West Indies, St. Augustine, Trinidad and Tobago;4. Department of Pharmaceutical Sciences, Mahatma Gandhi College of Pharmaceutical Sciences, Jaipur, Rajasthan, India;5. Faculty of Pharmacy, Philadelphia University, Amman, Jordan;6. School of Pharmacy and Pharmaceutical Sciences, Ulster University, Coleraine, County Londonderry, BT52 1SA, Northern Ireland, United Kingdom;7. Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia;8. Innovative Medicines Group, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia;9. Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, New South Wales, Australia;10. School of Pharmacy, Suresh Gyan Vihar University, Jaipur, Rajasthan, India |
| |
| Abstract: | The well-known condition of heart failure is a clinical syndrome that results when the myocardium's ability to pump enough blood to meet the body's metabolic needs is impaired. Most of the cardiac activity is maintained by adrenoceptors, are categorized into two main α and β and three distinct subtypes of β receptor: β1-, β2-, and β3-adrenoceptors. The β adrenoreceptor is the main regulatory macro proteins, predominantly available on heart and responsible for down regulatory cardiac signaling. Moreover, the pathological involvement of Angiotensin-converting enzyme 1 (ACE1)/angiotensin II (Ang II)/angiotensin II type 1 (AT1) axis and beneficial ACE2/Ang (1-7)/Mas receptor axis also shows protective role via Gi βγ, during heart failure these receptors get desensitized or internalized due to increase in the activity of G-protein-coupled receptor kinase 2 (GRK2) and GRK5, responsible for phosphorylation of G-protein-mediated down regulatory signaling. Here, we investigate the various clinical and preclinical data that exhibit the molecular mechanism of upset level of GRK change the cardiac activity during failing heart. |
| |
| Keywords: | beta adrenoreceptor chronic heart failure extracellular receptor kinase1/2 G-protein-coupled receptors GPCR kinases mitogen-activated protein kinase renin-angiotensin-aldosterone system |
|
|
