Hormone-activated guanylate cyclase

Diacylglycerol, on the other hand, is lipid soluble and remains in the lipid bilayer of the membrane. There it can activate protein kinase C (PKC), a very important and widely distributed enzyme which serves many systems through phosphorylation, including neurotransmitters (acetylcholine, a,- and P-adrenoceptors, serotonin), peptide hormones (insulin, epidermal growth hormone, somatomedin), and various cellular functions (glycogen metabolism, muscle activity, structural proteins, etc.), and also interacts with guanylate cyclase. In addition to diacylglycerol, another normal membrane lipid, phos-phatidylserine, is needed for activation of PKC. The DG-IP3 limbs of the pathway usually proceed simultaneously. 

Adenylate cyclase is a two-component enzyme system. It ultimately catalyzes the cyclase reaction, but only when it is associated with the hormone-bound receptor and a regulatory protein called a stimulatory G-protein (guanylate nucleotide binding protein), which activates adenylate cyclase. The G-protein is the intermediate between the receptor and the synthesis of cyclic AMP. 

Often the data cannot be related quantitatively to that obtained from studies with more highly organised systems, not only because of the altered circumstances of the adenylate cyclase (e.g. dilution effects, absence of endogenous inhibitors or activators), but also because of possible differences in the way the hormone is handled (e.g. metabolism, tissue uptake). As a rule, adenylate cyclase activity in broken cell preparations is less sensitive to hormonal stimulation than activity in intact cells [94], and guanylate cyclase activity does not respond to agents which increase the cyclic GMP level in intact cells [29]. 

Nitric oxide is made in the endothelial cells of the blood vessels. However, NO does not provoke a change in these cells. The hormone, occurring at concentrations of 10-1000 nAI, diffuses through the endothelial cel membrane and into nearby smooth muscle which encircles the blood ves.se (Beckman and Koppenol, 1996). Once inside the muscle cell, NO binds to guanylate cyclase, and activates it. Cuanylatfi cyclase catalyzes the conversion of GTP to cyclic GMP (cGMP), as shown here ... 

ANP is a polypeptide hormone that is secreted in large quantities by the atrial portion of the heart and from a variety of other mammalian cell types. It exerts many of its actions via activation of particulate guanylate cyclase [16, 134]. ANP is present in human follicular fluids [163] and specific ANP receptors have been identified in human spermatozoa [144]. Sperm chemotaxis to ANP was demonstrated by sperm accumulation in capillaries with ascending [6] and descending [192] gradients and by choice assays [192] (Table 4). It is not yet known whether ANP is involved in sperm chemotaxis in vivo and whether the physiological chemoattractant for human spermatozoa is an ANP-like substance. Since chemotaxis to ANP at physiological concentrations can be observed only in the presence of a neutral endopeptidase inhibitor such... 

As mentioned earlier, guanyl nucleotides have been found to play an important role In the activation of adenylate cyclase activity by many hormones (90, 91). The present observations show that in pars Intermedia tissue, GXP causes an almost doubling of the stimulatory effect of CRF while that of the B-adrenerglc ago-... 

Locate guanyl nucleotide-binding proteins (G proteins) in the cell and describe their structures, catalytic characteristics, and molecular mechanisms of activation and inactivation. Describe the roles of G proteins in coupling a hormone-receptor complex to adenylate cyclase and in amplifying the stimulus. 

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