Atrial natriuretic peptide/protein

Active tissue uptake and binding to intra- and extravascular proteins, however, can substantially increase the volume of distribution of peptide and protein drugs, as for example observed with atrial natriuretic peptide (ANP) [56]. 

Atrial natriuretic peptide (= ANP Atrial natriuretic factor ANF)] (protein) Animals ex stressed heart Activates PM GC (ANPR-A ANPR-B) - via NPR-A NPR-B (guanylyl cyclase-coupled receptors) induces plant stomatal opening inhibited by GC inhibitors LY83583 Methylene blue... 

Lavendustin A and derivatives have been used to study the pathophysiological role of protein kinases. For instance, lavendustin A was used to study the potential role of tyrosine kinases in the regulation of wall stretch-induced atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) secretion. Because lavendustin A is selective for t5n-osine kinases, the data obtained under these conditions showed that this kind of kinase is implicated in regulating cardiac hormone secretion. However, it is still unclear which tyrosine kinase is responsible for wall stretch-induced cardiac hormone secretion [111]. 

Cyclic nucleotide regulated protein kinase family = Adenylyl cyclases = A-kinase anchor proteins = Atypical PKCs = Atrial natriuretic peptide = Adenosine 5 -triphosphate = Brain natriuretic peptide = Ca Vcalmodulin-dependent kinases = Cyclin-dependent kinases = Ca -dependent protein kinase = Casein kinase I = Casein kinase II = Dcd-like kinase... 

Renal epithefial cell membranes also contain proteins that act as ion channels. For example, there is one for sodium that is closed by amiloride and modulated by hormones such as atrial natriuretic peptide (ANP). Ion channels enable much... 

An additional mechanism controlling lipolysis specifically in humans has recently come to light (J. Galitsky, 2000). Atrial natriuretic peptide has a potent stimulatory effect on lipolysis in human adipocytes, where administration of the peptide was associated with increased phosphorylation of HSL and perilipin. This effect was blocked by inhibition of cGMP-dependent protein kinase I. At this point it is unclear whether this kinase phospho-rylates HSL and perilipin directly or if it has an indirect effect mediated through PKA. 

For the receptors that bind atrial natriuretic peptides and the peptides guanylin and uroguanylin, the intracellular domain is not a protein kinase but rather a guanylyl cyclase that synthesizes the second messenger cyclic guanosine monophosphate (cyclic GMP), which activates a cyclic GMP-dependent protein kinase (PKG) and can modulate the activities of several cyclic nucleotide phosphodiesterases, among other effectors. 

Sarcevic, B., Brookes, V., Martin, T. J., et al. (1989). Atrial natriuretic peptide-dependent phosphorylation of smooth muscle cell particulate fraction proteins is mediated by cGMP-dependent protein kinase. J. Biol. Chem. 264, 20648-20654. 

Some receptors appear to be linked to the stimulation of guanylyl-cyclase. These membrane receptors mediate the action of the atrial natriuretic peptide (ANP), the heat-stable enterotoxin of E. coli and the receptors involved in fertilization in some species. These membrane receptors are glycoproteins of about 130-160 kDa spanning the membrane only once. The binding of the peptides occurs at the extracellular domain, while the intracellular regions contain both cyclase catalytic domains, converting GTP to cGMP, and a protein kinase-like domain. 

Thus, the volume of distribution of the central compartment in which peptides and proteins initially distribute after intravenous administration is typically 3 to 8 L, approximately equal to slightly higher than the plasma volume [19] (approximate body water volumes for a 70-kg person interstitial 12 L, intracellular 27 L, intravascular 3 L) [34]. The total volume of distribution (V ) is frequently 14 to 20 L, not more than twice the initial volume of distribution (Vc) [13, 28]. This distribution pattern has, for example, been described for the somatostatin analog octreotid (Vc 5.2-10.2 L, VIIIa inhibitor eptifibatide (Vc9.2 L) [35-37].Active tissue uptake and binding to intra- and extravascular proteins, however, can substantially increase the volume of distribution of peptide and protein drugs, as, for example, observed with atrial natriuretic peptide (ANP) [38]. 

The regulation of collagen synthesis in response to ascorbic acid has been the most extensively documented, as described above. Acetylcholine receptor, cytochrome P-450, atrial natriuretic peptide (ANP), and other proteins have also been demonstrated to respond to ascorbic acid with substantial changes in their transcripts. 

Fluorenyl-based reagent 58 has been used for the attachment of mPEG of up to 40 kDa to proteins by means of urethane bond formation (Scheme 3.11). The fluorenyl moiety releases the native unmodified protein at a slow controlled rate by hydrolysis reaction, as is shown in Equation 3.29 [216]. Reagent 58 has been used in the reversible PEGylation of exendine-4 [216], human growth hormone, interferon a2 [217], enkephalin [218], atrial natriuretic peptide [219] and insulin [220]. 

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