By Aldo Clerico, Michele Emdin
Modern cardiovascular technology has produced a innovative new proposal: the center acts now not in basic terms as a pump, yet as a "gland", that's as a regulator of circulatory homeostasis and salt-water stability. This ebook combines the classical heamodynamic view with the hot neuro-hormonal paradigm, in all its power medical implications. The e-book will curiosity physiologists and clinicians considering the examine of the cardiovascular method and care of middle patients.
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Although it probably binds ATP and contains many residues conserved in the catalytic domain of protein kinases, kinase activity has not been detected . It represses the enzyme activity of the catalytic cGMP-synthesizing domain and at the same time is necessary for its ligand-dependent activation . The coiled-coil hing region is involved in receptor dimerization, which is also essential for the activation of the catalytic domain . The cGMP produced modulates the activity of specific downstream regulatory proteins, such as cGMP-regulated phosphodiesterases, ion channels and cGMP-dependent Fig.
In contrast, other studies performed in cultured glomerular mesangial and renomedullary interstitial cells from the rat or Chinese hamster ovary cells reported that NPR-A is a constitutively membraneresident protein that neither undergoes endocytosis nor mediates lysosomal hydrolysis of ANP [188, 189]. A more recent study using 293T cells suggested that NPR-A and NPRB are neither internalized nor degraded in response to receptor occupation . Further studies are necessary to clarify whether or not ANP binding to NPR-A stimulates its internalization, and whether this process is tissue- and/or species-specific.
These studies suggest that normal ventricular myocardium may produce only a limited amount of BNP in response to an acute and appropriate stimulation, probably via a constitutive secretory pathway, while the amount of hormone produced and secreted after chronic stimulation could be greatly increased via an upregulated secretory pathway. However, further studies are necessary in order to confirm the presence of secretory granules in human ventricular cardiomyocytes and in particular to evaluate their peptide content and pathophysiological relevance.