AMP, cyclic levels

O Neill, C., Riddle, P., Rosengurt, E. (1985). Stimulating the proliferation of quiescent 3T3 fibroblasts by peptide growth factors or by agents which elevate cellular cyclic AMP level has opposite effects on motility. Expt. Cell Res. 156.65-78. 

Chin CN, Lucas-Lenard J, Abadji V, Kendall DA. Ligand binding and modulation of cyclic AMP levels depend on the chemical nature of residue 192 of the human cannabinoid receptor 1. J Neurochem 1998 70 366-373. 

We have tested the hypothesis that insulin inhibits the stimulatory effect of parathyroid hormone (PTH) on calcium reabsorption in the distal nephron. PTH is known to enhance calcium transport in renal cells, probably by stimulation of adenylate cyclase and subsequent increases in 3 5 cyclic AMP productoin. Since insulin had been observed to inhibit PTH-stimulated increases in kidney cyclic AMP levels in vitro (24) we investigated whether insulin-mediated hypercalciuria was dependent on the presence of PTH in vivo. 

Abrams DB, Monti PM, Carey KB, Pinto RP, Jacobus SI (1988) Reactivity to smoking cues and relapse two studies of discriminant validity. Behav Res Ther 26(3) 225-233 American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders, 4th edn (DSM-IV). American Psychiatric Association, Washington, DC Asghari V, Sanyal S, Buchwaldt S, Paterson A, Jovanovic V, Van Tol HH (1995) Modulation of intracellular cyclic AMP levels by different human dopamine D4 receptor variants. J Neurochem 65(3) 1157-1165... 

Figure 6.34 Effects of glucagon and insulin on the cyclic AMP level. Glucagon increases the activity of adenylate cyclase, which increases the concentration of cyclic AMP whereas insulin activates the phosphodiesterase which hydrolyses cyclic AMP to form AMP. Cyclic AMP activates protein kinase A.

Stimulation of the parasympathetic system releases acetylcholine at the neuromuscular junction in the sinoatrial node. The binding of acetylcholine to its receptor inhibits adenylate cyclase activity and hence decreases the cyclic AMP level. This reduces the heart rate and hence reduces cardiac output. This explains why jumping into very cold water can sometimes stop the heart for a short period of time intense stimulation of the vagus nerve (a parasympathetic nerve) markedly increases the level of... 

Several methyixanthines produced by plants are inhibitors of cyclic AMP phosphodiesterase and thereby produce an elevation in cyclic AMP levels in cells throughout the body. 

C. Aspirin inhibits platelet cyclooxygenase. Abciximab, a monoclonal antibody, binds to and inhibits the platelet glycoprotein Ilb/IIIa receptor. Dipyridamole inhibits platelet cyclic AMP phosphodiesterase and raises cyclic AMP levels. Eptifibatide binds to the glycoprotein Ilb/IIIa complex. 

The TET-induced inhibitory influence on cyclic 3 ,5 -AMP phosphodiesterase (PDE) activities precedes edema formation in the rat brain [74]. lb clarify the mechanism of the protective action of EGb against TET-toxidty in rats, in vitro and ex vivo effects of EGb on PDE activities of cerebral tissue were investigated [75]. Higher concentrations of EGb (5-250 mg/L) inhibited the PDE activity in the brain in normal rats, whereas lower concentrations (0.25-4.0 mg/L) of EGb enhanced the activity of the enzyme. The inhbitory effect of TET on the high affinity PDE activity (measured with 0.25 ftM cyclic AMP) of the brain was diminished in the presence of low EGb concentrations. Furthermore, preventive and curative treatment of 1 El-poisoned rats with EGb (100 mg/kg, p.o., for 7 days) prevented both the formation of edema and the fall of PDE activity induced by TET alone. These results suggested the antiedema action of EGb might be partly associated with its modulating influences on cellular cyclic AMP levels via activation of membrane-bound PDE. 

Auchampach JA, Jin X, Wan TC, Caughey GH, Linden J (1997) Canine mast cell adenosine receptors cloning and expression of the A3 receptor and evidence that degranulation is mediated by the A2B receptor. Mol Pharmacol 52(5) 846-860 Aune TM, McGrath KM, Sarr T, Bombara P, Kelley KA (1993) Expression of 5HTla receptors on activated human T cells. Regulation of cyclic AMP levels and T cell proliferation by 5-HT. J Immunol 151 (3) 1175-1183... 

In recent work on CHO cells, it had been suggested that the effects of butyrate are mediated by cyclic AMP (18). We found, however, that cyclic AMP (2 mM), its mono- (1 mM and dibutyryl (0.5 mM) derivatives, theophylline and prostaglandins did not cause an elevation in si alyl transferase activity (1). Choleragen, which is a potent and persistant activator of adenylate cyclase (see below), also did not elevate sialyl transferase activity in HeLa cells (Table I) or alter cell morphology (unpublished observations). Thus, it is unlikely that these effects of butyrate are mediated by elevation of cyclic AMP levels. 

Cyclic AMP assay. Cyclic AMP levels were measured on 6% cold trichloracetic acid extracts of sonicated cell extracts as described previously (14). The succinylated tyrosyl derivative of cyclic AMP... 

Since Nirenberg and his collaborators (5,6,11) have reported that in NG108-15 cells, opiates produce an initial inhibition of cyclic AMP synthesis (0 to 30 min), followed by a period in which the cell adjusts and cyclic AMP levels return to normal (lO -30 hrs), and finally a period where cyclic AMP levels are elevated (when the drug is removed or metabolized supposed withdrawal) it was of interest to follow the time-course of the inhibition. 

The addition of phosphodiesterase inhibitors such as isobutylmethylxanthine (IBMX) and cyclic AMP analogs such as the 8-bromo- and dibutyryl-derivatives resulted in a stimulation of synthesis which could not be blocked by the co-addition of opiates. This implies that opiates are exerting their effect at the level of adenylate cyclase activation. The actual effect of these drugs on cellular cyclic AMP levels was determined by radioimmunoassay as shown in Table III. 

If a direct correlation between ganglioside synthesis and cyclic AMP levels does in fact exist then a hypothesis must be developed to explain it. Based on our current level of understanding, the most plausible hypothesis involves linking the two phenomena by a... 

N4TG1 cells were exposed to drugs for 10 min and the cyclic AMP level determined by radioimmunoassay as described in the text. 

TABLE IV. Modulation of Cyclic AMP levels in neuroblastoma cells is directly related to ganglioside synthesis... 

The role of cyclic AMP as modulator of prolactin secretion was first suggested by the finding of a stimulatory effect of cyclic AMP derivatives (17-22) and inhibitors of cyclic nucleotide phosphodiesterase activity such as theophylline and IBMX (22-26) on the secretion of this hormone. More convincing evidence supporting a role of cyclic AMP in the action of dopamine on prolactin secretion had to be obtained, however, by measurement of adenohypophysial adenylate cyclase activity or cyclic AMP accumulation under the influence of the catecholamine. As illustrated in Fig. 1, addition of 100 nM dopamine to male rat hemipituitaries led to a rapid inhibition of cyclic AMP accumulation, a maximal effect (30% inhibition) being already obtained 5 min after addition of the catecholamine. Thus, while dopamine is well known to stimulate adenylate cyclase activity in the striatum (27, 28), its effect at the adenohypophysial level in intact cells is inhibitory. Dopamine has also been found to exert parallel inhibitory effects on cyclic AMP levels and prolactin release in ovine adenohypophysial cells in culture (29) and purified rat mammotrophs (30). Using paired hemipituitaries obtained from female rats, Ray and Wallis (22) have found a rapid inhibitory effect of dopamine on cyclic AMP accumulation to approximately 75% of control. 

As illustrated in Fig. 3A, dopamine leads to a 30% (p <0.01) inhibition of basal cyclic AMP levels in pars intermedia cells at an EDgg value of 5.0 nM. An almost identical potency of dopamine is observed on the elevated cyclic AMP concentration induced by simultaneous incubation with 30 nM (-)isoproterenol (Fig. 3B). Similar inhibitory effects of dopamine are observed in the presence of a phosphodiesterase inhibitor, isobutylmethylxanthine, thus... 

Figure 3. Effect of increasing concentrations of dopamine on basal (A) and (—fisoproterenol-induced (B) cyclic AMP levels in rat pars intermedia cells in culture. Cells were incubated for 30 min in DMEM containing 5 mM HEPES, 100 pM ascorbic acid, and the indicated concentrations of dopamine alone (A). In B, 30 nM (—(isoproterenol was present during the last 4 min of incubation. Data are expressed as percent of control (in the absence of dopamine). Control cyclic AMP levels were 0.96 0.10 and 5.29 0.13 pmol/2 X 10s cells in the absence (A) or presence (B) of 30 M (—(isoproterenol, respectively (41).

Dopamine can thus be added to the list of hormones and neurotransmitters which can stimulate or inhibit cyclic AMP formation, depending upon their tissue of action. Thus, while dopamine stimulates cyclic AMP formation in parathyroid cells, superior cervical ganglia, retina and striatal tissue (27, 58-61), it inhibits the accumulation of the cyclic nucleotide in cells of the intermediate and anterior lobes of the pituitary gland. Opposite effects on the cyclic AMP system are also found with LHRH which stimulates and inhibits cyclic AMP levels in the anterior pituitary gland (62) and ovary (63), respectively. Similarly, alpha-adrenergic agents show opposite effects on cyclic AMP formation in brain (64) and platelets (65). PGE, stimulates cyclic AMP formation in the anterior pituitary gland (62) while it inhibits the same parameter in fat cells (66). 

The above-described data show that CRF added to cells of the rat Intermediate lobe In culture causes a rapid stimulation of oe-MSH release and cyclic AMP accumulation, thus demonstrating a direct action of the peptide on pars intermedia cells (15). It is however difficult, using intact cells, to dissociate between increases in cyclic AMP levels due to stimulation of adenylate cyclase activity or to Inhibition of cyclic nucleotide phosphodiesterase or to a combination of both effects. Definitive proof of the role of adenylate cyclase In the action of CRF In the intermediate lobe of the pituitary gland is provided by the following findings of a CRF-lnduced stimulation of adenylate cyclase activity in homogenate of rat and bovine pars Intermedia cells. 

The present data clearly demonstrate that the 41-amino acid ovine CRF Is a potent stimulator of adenylate cyclase activity In rat and bovine pars Intermedia tissue. Our previous data have shown that CRF causes a rapid and marked stimulation of cyclic AMP accumulation in rat pars Intermedia cells in culture (15). The final proof of the role of adenylate cyclase in the observed changes of cyclic AMP levels had to be obtained by direct measurement of adenylate cyclase activity. 

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