CAMP stimulation

In contrast, functional assays that look at post-receptor events, such as cAMP stimulation (Gs), cAMP inhibition (G ), inositol triphosphate (IP3)/mono-phosphate (IP1) increase (Gq), or intracellular calcium mobilization (Gq), are homogeneous, for the most part nonradioactive, and easy to automate (with... 

Br > Cl > I. This conductance was not time-dependent. On the other hand, Cl conductance stimulated by the Ca2+ ionophore A23187 (2.5 pM) or elevation in the free Ca2+ levels in the pipet from 100 to 500 nM was time-dependent and exhibited a nonlinear current-voltage relationship that was outwardly rectifying. The permselectivity of this Ca2+-stimulated conductance was 1 > Br > cr, distinguishing it from the cAMP-stimulated Cfr conductance. As both calcium ionophore A23187 and cAMP were shown to elevate the Cl conductance of the cornea, it is quite likely that these two types of Cr channels are present in the corneal epithelium [96,106,114],... 

A few enzymes, such as the previously mentioned CNP, are believed to be fairly specific for myelin/oligodendro-cytes. There is much more in the CNS than in peripheral nerve, suggesting some function more specialized to the CNS. In addition, a unique pH 7.2 cholesterol ester hydrolase is also enriched in myelin. On the other hand, there are many enzymes that are not myelin-specific but appear to be intrinsic to myelin and not contaminants. These include cAMP-stimulated kinase, calcium/calmodulin-dependent kinase, protein kinase C, a neutral protease activity and phosphoprotein phosphatases. The protein kinase C and phosphatase activities are presumed to be responsible for the rapid turnover of MBP phosphate groups, and the PLP acylation enzyme activity is also intrinsic to myelin. 

Any of a broad class of phosphoryl-transfer enzymes [EC 2.7.1.x] that catalyze the ATP-dependent phosphorylation of proteins, most often occurring at seryl, threo-nyl, and tyrosyl residues. These enzymes are central participants in cellular signal transduction pathways, and their discovery and recognition as primary control components of the cell culminated in the award of the 1992 Nobel Prize in Medicine and Physiology to American enzymologists Edwin Krebs and Edward Fischer. There is reason to believe that approximately 2% of the coding sequences in the human genome specify some 2000 different kinases that phosphorylate protein substrates. The prototypical enzyme is known as 3, 5 -cAMP-stimulated protein kinase (or, protein kinase A). See specific protein kinase... 

Of the protein kinases, protein kinase A is the best investigated and characterized (review Francis and Corbin, 1994). The functions of protein kinase A are diverse. Protein kinase A is involved in the regulation of metabolism of glycogen, lipids and sugars. Substrates of protein kinase A may be other protein kinases, as well as enzymes of intermediary metabolism. Protein kinase A is also involved in cAMP-stimulated transcription of genes that have a cAMP-responsive element in their control region (review Montminy, 1997). An increase in cAMP concentration leads to activation of protein kinase A which phosphorylates the transcription factor CREB at Ser 133. CREB only binds to the transcriptional coactivator CBP in the phosphorylated state and stimulates transcription (see Chapter 1.4.4.2). 

These are among the most powerful, but prolonged use can aggravate constipation. Mechanisms of action are muitipie and not well studied. They include increased permeability of the mucosa leading to accumuiation of water in the lumen, inhibition of intestinal Na+,K-i-ATPase, and increased synthesis of prostagiandins and cAMP. Stimulant laxatives include the following. 

When the hormonal stimulus stops, the intracellular actions of cAMP are terminated by an elaborate series of enzymes. cAMP-stimulated phosphorylation of enzyme substrates is rapidly reversed by a diverse group of specific and nonspecific phosphatases. cAMP itself is degraded to 5 -AMP by several cyclic nucleotide phosphodiesterases (PDE Figure 2-13). Competitive inhibition of cAMP degradation is one way caffeine, theophylline, and other methylxanthines produce their effects (see Chapter 20). 

Apart from exocytosis, presynaptic H3 autoreceptors also inhibit the synthesis of histamine at the level of nerve endings, at least in part through pathways distinct from those leading to the inhibition of release. One pathway is inhibition of adenylyl cyclase (Gomez-Ramirez et al. 2002 Moreno-Delgado et al. 2006) activation of cAMP-dependent protein kinase A by cAMP stimulates histamine synthesis through phosphorylation of histidine decarboxylase, and this stimulation is diminished when adenylyl cyclase activity decreases following activation of H3 autoreceptors and Gi/o proteins. 

There are three important ADP receptors on the platelet surface (16). The P2X, inotrophic receptor is responsible for rapid influx of calcium into the cytosol. The P2Y, receptor mediates mobilization of calcium through activation of PLC and shape change. The P2Y,2 receptor is coupled to adenyl cyclase inhibition mediated by a G-protein with subsequent decrease in the cAMP The decrease in cAMP stimulates dephosphorylation of VASP that is closely correlated with the GPIIb/llla activation. 

Soroker and Rafaeli, 1995). This confirmed that calcium is involved in pheromone biosynthesis and that there is a cross-talk between the two messengers, since the increase in calcium, as a result of the ionophores, induced the increase in cAMP. This reinforces the hypothesis that cAMP stimulation occurs downstream of the calcium influx (Jurenka et al., 1991c Soroker and Rafaeli, 1995). 

Figure 5. Comparison of the potency of isoproterenol in eliciting physiological and biochemical responses from the rat IL. Substantially lower concentrations of isoproterenol stimulate the release of IR-aMSH (aMSH) than are required to enhance cAMP accumulation by intact IL cells (cAMP), stimulate adenylate cyclase activity in cell-free homogenates of IL tissue (cyclase), or occupy the specific binding sites defined with IHYP (binding) (19).

Davis BJ, Weaver R, Gaines LJ, et al. 1994b. Mono-(2-ethylhexyl) phthalate suppresses estradiol production independent of FSH-cAMP stimulation in rat granulosa cells. Toxicol Appl Pharmacol 128 224-228. 

Glucagon and exogenous cAMP stimulate the Na+-dependent transport of alanine and certain other amino acids into the perfused liver [176] and isolated hepa-tocytes [177-179], There is a rapid initial stimulation of the transport [177, 178] which is probably related to the stimulation of (Na2+-K+)-ATPase activity and membrane hyperpolarization [177], This is followed after 30-90 min by a larger increase which is blocked by cycloheximide [178]. Kinetic analysis indicates that both the short and long term actions of glucagon result in an increase in the Vmax for transport [177,179,180], and it has been proposed that the slower effect is due to the synthesis of a high affinity amino acid transport component [179,180],... 

Intracellular cyclic adenosine monophosphate (cAMP)-stimulated add secretion in the isolated guinea-pig gastric mucosa was not inhibited by administration of an H2-receptor antagonist, as expected, although H 83/69 (timoprazole) induced a dose-dependent inhibition. This was the first experimental evidence for a site of inhibitory action beyond the panel of stimulatory cell membrane receptors. Interestingly, it was found that the initial lead compound (CMN 131), had no inhibitory effect on dibutyryl-cAMP-stimulated acid secretion, nor was it an H2-receptor antagonist [9],... 

Li D, et al. cAMP-Stimulated Interaction Between Steroidogenic 100. Factor-1 and Diacylglycerol Kinase-theta Facilitates Induction of CYP17. Mol. Cell Biol. 2007. 

DE CHAFFOY DE COURCELLES D, ROEVENS P, Belle H. Agents that devate platdet cAMP stimulate the formation of pbosphaddylinositol 4-phosphate in intact human platdets FEBSLett 195 115-118,1986. 

Muscle glycogen is utilized to generate ATP for muscle contraction. -Epinephrine, via cAMP, stimulates muscle glycogen breakdown. 

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