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PubMed2002

The coactivator PGC-1 is involved in the regulation of the liver carnitine palmitoyltransferase I gene expression by cAMP in combination with HNF4 alpha and cAMP-response element-binding protein (CREB).

Liver carnitine palmitoyltransferase I catalyzes the transfer of long-chain fatty acids into mitochondria. L-CPT I is considered the rate-controlling enzyme in fatty acid oxidation. Expression of the L-CPT I gene is induced by starvation in response to glucagon secretion from the pancreas, an effect mediated by cAMP. Here, the molecular mechanisms underlying the induction of L-CPT I gene expression by cAMP were characterized. We demonstrate that the cAMP response unit of the L-CPT I gene is composed of a cAMP-response element motif and a DR1 sequence located 3 kb upstream of the transcription start site. Our data strongly suggest that the coactivator PGC-1 is involved in the regulation of this gene expression by cAMP in combination with HNF4 alpha and cAMP-response element-binding protein (CREB). Indeed, (i) cotransfection of CREB or HNF4 alpha dominant negative mutants completely abolishes the effect of cAMP on the L-CPT I promoter, and (ii) the cAMP-responsive unit binds HNF4 alpha and CREB through the DR1 and the cAMP-response element sequences, respectively. Moreover, cotransfection of PGC-1 strongly activates the L-CPT I promoter through HNF4 alpha bound at the DR1 element. Finally, we show that the transcriptional induction of the PGC-1 gene by glucagon through cAMP in hepatocytes precedes that of L-CPT-1. In addition to the key role that PGC-1 plays in glucose homeostasis, it may also be critical for lipid homeostasis. Taken together these observations suggest that PGC-1 acts to coordinate the process of metabolic adaptation in the liver.

Animals↗

PubMed1992

cAMP-induced desensitization of surface cAMP receptors in Dictyostelium: different second messengers mediate receptor phosphorylation, loss of ligand binding, degradation of receptor, and reduction of receptor mRNA levels.

Surface cAMP receptors on Dictyostelium cells are linked to several second messenger systems and mediate multiple physiological responses, including chemotaxis and differentiation. Activation of the receptor also triggers events which desensitize signal transduction. These events include the following: 1) loss of ligand binding without loss of receptor protein; 2) phosphorylation of the receptor protein, which may lead to impaired signal transduction; 3) redistribution and degradation of the receptor protein; and 4) decrease of cyclic AMP (cAMP) receptor mRNA levels. These mechanisms of desensitization were investigated with the use of mutant synag7, with no activation of adenylyl cyclase; fgdC, with no activation of phospholipase C; and fgdA, with defects in both pathways. cAMP-induced receptor phosphorylation and loss of ligand binding activity was normal in all mutants. In contrast, cAMP-induced degradation of the receptor was absent in all mutants. The cAMP-induced decrease of cAMP-receptor mRNA levels was normal in mutant synag7, but absent in mutant fgdC. Finally, the cAMP analogue (Rp)-cAMPS induced loss of ligand binding without inducing second messenger responses or phosphorylation, redistribution, and degradation of the receptor. We conclude that 1) loss of ligand binding can occur in the absence of receptor phosphorylation; 2) loss of ligand binding and receptor phosphorylation do not require the activation of second messenger systems; 3) cAMP-induced degradation of the receptor may require the phosphorylation of the receptor as well as the activation of at least the synag7 and fgdC gene products; and 4) cAMP-induced decrease of receptor mRNA levels requires the activation of the fgdC gene product and not the synag7 gene product. These results imply that desensitization is composed of multiple components that are regulated by different but partly overlapping sensory transduction pathways.

Animals↗

PubMed1981

Activation of cAMP-dependent protein kinase in epidermis by the compounds which increase epidermal cAMP.

Pig epidermal slices were incubated with various compounds which increased epidermal cAMP (adenosine 3',5'-monophosphate), and the change in cAMP-dependent protein kinase activity ratio was studied by the method of Cherrington et al (J Biol Chem 251:5209-5218, 1976) with modification. Epinephrine (5 x 10(-5) M), histamine (10(-4) M) and adenosine (10(-3) M), potent agonists of epidermal adenyl cyclase, fully activated the protein kinase (PK) during an incubation of 30 to 45 seconds, that was much shorter than that required for maximal cAMP accumulation under the same conditions (5 min). With such a brief stimulus, the epidermal cAMP-PK system did not become refractory and responded to repeated stimuli. Prostaglandin E2 (PGE2) and isobuthylmethylxanthine (IBMX) and ethanol only partially activated the enzyme. Prostaglandin F2 alpha (PGF2 alpha) and theophylline which were much less effective in increasing epidermal cAMP, activated the enzyme to the same extent as PGE2 and IBMX respectively. These results suggest that protein kinase activation takes place in response to a cAMP increase in small locus of the cell. Such an increase in cAMP can be very small or even not measurable when measured as total cAMP in the tissue homogenate. Also, increases above this level may not be physiologic. It is concluded that measurement of cAMP-dependent protein kinase activity ratio is a more direct and more sensitive way to study the effect of compounds which act through cAMP mediated mechanisms.

Adenosine↗

PubMed1994

Regulation of VLDL secretion in primary culture of rat hepatocytes: involvement of cAMP and cAMP-dependent protein kinases.

When hepatocytes were cultured for 24 h in the presence of forskolin (10(-4) mol l-1) or isobutylmethylxanthine (IBMX, 10(-3) mol l-1), the intracellular cAMP concentration peaked (320-380 pmol mg-1 protein) after 10-20 min of culture. This increase was accompanied by a decrease in the secretion of triacylglycerol, cholesterol and apoprotein B associated with VLDL. After 4 h cAMP levels had returned almost to basal values but the inhibition of VLDL secretion persisted. There was a small intracellular accumulation of triacylglycerol but not of apoprotein B. Addition of forskolin and IBMX together led to a further increase in intracellular cAMP and a further suppression of VLDL output. Similar effects on the secretion of VLDL were also observed after addition of Bt2cAMP. Exposure of cell cultures to glucagon (10(-7) mol l-1) for only 10 min raised cellular cAMP levels to > 200 pmol mg-1 protein, and suppressed VLDL secretion during the next 24 h to < 40% of control. All of the substances tested inhibited de novo synthesis of fatty acids but had little or no effect on cholesterol synthesis and did not inhibit oleate esterification to triacylglycerol. The cAMP-dependent protein kinase antagonist Rp-cAMPS prevented suppression of VLDL triacylglycerol secretion induced by glucagon (10(-7) mol l-1) and abolished glucagon-induced ketogenesis. Rp-cAMPS also inhibited Bt2cAMP (7.5 x 10(-6) mol l-1)-induced suppression of VLDL secretion and enhancement of ketogenesis. It is concluded that rat hepatic VLDL metabolism can be regulated by cAMP and cAMP-dependent protein kinases, and that the initial transient rise in cellular cAMP levels induced by glucagon is sufficient to maintain a long-term inhibitory effect on assembly and secretion of VLDL.

Animals↗

PubMed1992

Lithium, an inhibitor of cAMP-induced inositol 1,4,5-trisphosphate accumulation in Dictyostelium discoideum, inhibits activation of guanine-nucleotide-binding regulatory proteins, reduces activation of adenylylcyclase, but potentiates activation of guanylyl cyclase by cAMP.

Li+ drastically alters pattern formation in Dictyostelium by inhibiting cAMP-induced prespore-gene expression and promoting cAMP-induced prestalk-gene expression. We reported previously that Li+ inhibits inositol monophosphatases in this organism and strongly reduces basal and cAMP-stimulated inositol 1,4,5-trisphosphate levels. We show here that Li+ also reduces cAMP-induced accumulation of cAMP, but promotes cAMP-induced accumulation of cGMP. This effect is not due to inhibition of cGMP hydrolysis or inhibition of adaptation and may therefore reflect stimulation of guanylyl-cyclase activation. Li+ does not affect the binding of cAMP to surface receptors but interferes with the interaction between receptors and guanine-nucleotide-binding regulatory (G) proteins. These effects are complex; in the absence of Mg2+, Li+ increases guanosine 5'-[gamma-thio]triphosphate(GTP[S])-binding activity to similar levels as 1 mM Mg2+. However, while Mg2+ potentiates cAMP-induced stimulation of GTP[S]-binding activity, Li+ effectively inhibits stimulation. Li+ also inhibits cAMP-stimulated, but not basal high-affinity GTP-ase activity, indicating an inhibitory effect on cAMP-induced activation of G-proteins. Our data suggest that in addition to inositolphosphate metabolism, the activation of G-proteins may be a second biochemical target for Li+ effects on pattern formation and signal transduction in Dictyostelium.

Adenylyl Cyclases↗

PubMed1984

Adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase activity in rodent pituitary tissue: possible role in cAMP-dependent hormone secretion.

A cAMP-dependent protein kinase occurs in the intermediate lobe of the rat pituitary gland and the ACTH-secreting tumor AtT-20/D16-16 derived from the mouse pituitary gland. Exposure of either tissue to drugs increasing cAMP production and hormone release (forskolin, cholera toxin, or isoproterenol in the case of the intermediate lobe; forskolin or isoproterenol in the case of the AtT-20 cells) increases the cAMP-dependent protein kinase activity of a tissue homogenate in the absence, but not in the presence, of added cAMP. The potencies of these drugs to induce changes in the protein kinase activity ratio (i.e. enzyme activity in the absence of cAMP to enzyme activity in the presence of 3 microM cAMP) are comparable with their potencies as stimulants of hormone secretion. In either tissue, A23187, a calcium ionophore that stimulates hormone release but not cAMP production, does not change the protein kinase activity ratio. In the case of the AtT-20 cells, dexamethasone blocks the release of ACTH simulated by either isoproterenol or forskolin, but does not alter the enhancement of protein kinase activity induced by these drugs. Conversely, dexamethasone does not block the A23187-stimulated release of ACTH. The data suggest that cAMP modulates (but does not trigger) hormone secretion from the rodent pituitary gland by a mechanism involving activation of the cAMP-dependent protein kinase. Several possible sites for this modulatory effect of cAMP are discussed.

Adrenocorticotropic Hormone↗

PubMed1988

High density lipoproteins stimulate placental lactogen release and adenosine 3',5'-monophosphate (cAMP) production in human trophoblast cells: evidence for cAMP as a second messenger in human placental lactogen release.

Recent studies from our laboratory indicate that high density lipoproteins (HDL) and apolipoproteins-AI, -AII, and -CI stimulate the release of human placental lactogen (hPL) from human placental explants and trophoblast cells. However, the intracellular mechanisms by which HDL stimulate hPL release are unknown. Since earlier investigations from our laboratory indicated that pharmacological agents that increase intracellular cAMP levels [such as (Bu)2cAMP, isobutylmethylxanthine, and cholera toxin] also stimulate hPL release, we have performed studies to determine whether the stimulation of hPL release by HDL may be mediated by cAMP. Exposure of an enriched fraction of enzymatically dispersed hPL-producing cells to HDL (10-1500 micrograms/ml) for 0.5 h resulted in a significant dose-dependent stimulation of both cAMP production and hPL release. The half-maximal effective HDL dose for cAMP production and hPL release was 60-100 micrograms/ml. When perifused trophoblast cells were exposed to HDL (150 micrograms/ml) for 25 min, the increase in cAMP production preceded the increase in hPL release. The increase in cAMP production occurred during the first 5 min of exposure to HDL and reached a maximum (12.1 +/- 1.6-fold greater than base-line levels) 10 min after exposure. The increase in hPL release occurred about 10 min after the initial increase in cAMP production, reaching a maximum (9.7 +/- 1.4-fold greater than base-line levels) 15 min after exposure to HDL. HDL (300 micrograms/ml) also stimulated a 2.7-fold (P less than 0.001) increase in adenylate cyclase activity in placental plasma membranes, a magnitude of stimulation comparable to that caused by epinephrine (1 mM). Apolipoprotein-AII stimulated cAMP formation and hPL release in trophoblast cells with a pattern identical to that of HDL. These results, the first to demonstrate an effect of HDL on adenylate cyclase activity and cAMP production, strongly suggest a role for cAMP as a second messenger in HDL-stimulated hPL release.

Apolipoproteins↗

PubMed2000

Novel cyclic adenosine 3',5'-monophosphate (cAMP) response element modulator theta isoforms expressed by two newly identified cAMP-responsive promoters active in the testis.

cAMP signaling contributes to the control of the developmental progression of germ cells during the spermatogenic cycle. Genes regulated by cAMP include those encoding transcription factors such as the cAMP-responsive element modulator (CREM). The disruption of CREM gene expression in crem null mice results in arrest of spermatogenesis and infertility. The transcriptional control of the CREM gene is attributed to two promoters, P1 and P2. The P1 promoter constitutively activates the synthesis of messenger RNAs encoding activator (tau) and repressor (alpha) forms of CREM, whereas the cAMP-responsive P2 promoter activates the formation of messenger RNAs encoding the inducible cAMP early repressor. Here we report the identification of two additional promoters in the CREM gene, P3 and P4, that in the rat testis encode two novel transcriptional activator CREM isoforms, termed CREM theta1 and CREM theta2, respectively. Notably, the P3 and P4 promoters are activated by cAMP-dependent protein kinase, thereby providing cAMP-regulated transcription of CREM activators in addition to the established cAMP-regulated inducible cAMP early repressor. Analysis ex vivo of CREM gene expression in temporally staged segments of the seminiferous tubule during the spermatogenic cycle shows that the activities of the P1, P3, and P4 promoters are independently regulated. Our identification of the cAMP-activated P3 and P4 promoters that direct expression of the novel theta1 and theta2 activator isoforms of CREM brings further insight into the complex expression of the CREM gene during germ cell development and may have implications in understanding the control of fertility.

Amino Acid Sequence↗

PubMed1989

Plasmids encoding PKI(1-31), a specific inhibitor of cAMP-stimulated gene expression, inhibit the basal transcriptional activity of some but not all cAMP-regulated DNA response elements in JEG-3 cells.

Plasmids that encode a bioactive amino-terminal fragment of the heat-stable inhibitor of the cAMP-dependent protein kinase, PKI(1-31), were employed to characterize the role of this protein kinase in the control of transcriptional activity mediated by three DNA regulatory elements in the JEG-3 human placental cell line. The 5'-flanking sequence of the human collagenase gene contains the heptameric sequence, 5'-TGAGTCA-3', previously identified as a "phorbol ester" response element. Reporter genes containing either the intact 1.2-kilobase 5'-flanking sequence from the human collagenase gene or just the 7-base pair (bp) response element, when coupled to an enhancerless promoter, each exhibit both cAMP and phorbol ester-stimulated expression in JEG-3 cells. Cotransfection of either construct with plasmids encoding PKI(1-31) inhibits cAMP-stimulated but not basal- or phorbol ester-stimulated expression. Pretreatment of cells with phorbol ester for 1 or 2 days abrogates completely the response to rechallenge with phorbol ester but does not alter the basal expression of either construct; cAMP-stimulated expression, while modestly inhibited, remains vigorous. The 5'-flanking sequence of the human chorionic gonadotropin-alpha subunit (HCG alpha) gene has two copies of the sequence, 5'-TGACGTCA-3', contained in directly adjacent identical 18-bp segments, previously identified as a cAMP-response element. Reporter genes containing either the intact 1.5 kilobase of 5'-flanking sequence from the HCG alpha gene, or just the 36-bp tandem repeat cAMP response element, when coupled to an enhancerless promoter, both exhibit a vigorous cAMP stimulation of expression but no response to phorbol ester in JEG-3 cells. Cotransfection with plasmids encoding PKI(1-31) inhibits both basal and cAMP-stimulated expression in a parallel fashion. The 5'-flanking sequence of the human enkephalin gene mediates cAMP-stimulated expression of reporter genes in both JEG-3 and CV-1 cells. Plasmids encoding PKI(1-31) inhibit the expression that is stimulated by the addition of cAMP analogs in both cell lines; basal expression, however, is inhibited by PKI(1-31) only in the JEG-3 cell line and not in the CV-1 cells. These observations indicate that, in JEG-3 cells, PKI(1-31) is a specific inhibitor of kinase A-mediated gene transcription, but it does not modify kinase C-directed transcription.(ABSTRACT TRUNCATED AT 400 WORDS)

1-Methyl-3-isobutylxanthine↗

PubMed1988

Molecular cloning and cell-specific expression of newly discovered subunits of cAMP-dependent protein kinases. Implications for different cellular responses to cAMP.

In recent years a multiplicity in isoforms of cAMP-dependent protein kinases has been revealed. Gene products for four different regulatory subunits (RI alpha, RI beta, RII alpha, RII beta) and two different catalytic subunits (C alpha, C beta) have been identified. We hereby present the molecular cloning of rat cDNAs for RII beta, as well as full-length human cDNAs for RII beta and RI alpha. The amino acid sequences deduced from the cDNAs of the regulatory subunits, revealed dissimilarities which were primarily confined to the N-terminal part of the protein. Based on the vital role in testicular function played by gonadotropin-induced activation of cAMP-dependent protein kinases, mRNA levels for the various subunits of cAMP-dependent protein kinase have been studied in rat testis. A clear pattern of cellular localization of mRNAs for the various subunits of cAMP-dependent protein kinase has been demonstrated. Furthermore, stimulation of Sertoli cells by FSH and cAMP elicited a differential response in mRNA levels for various subunits. A dramatic increase (30-40 fold) in the mRNA for RII beta (3.2 kb) was seen with cAMP stimulation, whereas such treatment had minor effects on mRNAs for RI alpha, RII alpha and C alpha. A distinct pattern of expression for various subunits of cAMP-dependent protein kinase was observed during germ cell differentiation. RI alpha and RI beta were expressed at high levels at early stages of spermatogenesis, whereas unique mRNAs for RII alpha and RII beta appeared in post-meiotic germ cells. Altogether, the present results demonstrate specific expression of mRNAs for different subunits of cAMP-dependent protein kinase in different cell types, during hormonal stimulation and during cellular differentiation. This indicates that the individual subunits may confer specific functional properties to the cAMP-dependent protein kinase holoenzyme and to the cAMP signal pathway of the cell.

Animals↗

PubMed1988

Deletion of cAMP-binding site B in the regulatory subunit of cAMP-dependent protein kinase alters the photoaffinity labeling of site A.

Photoaffinity labeling with 8-azidoadenosine 3':5'-monophosphate is a highly selective method for probing the cAMP-binding sites of the regulatory subunits of cAMP-dependent protein kinase and for identifying specific residues that are in close proximity to the cAMP-binding sites. The cAMP-binding site of a mutant RI-subunit has been characterized here and contrasted to the native RI-subunit. This mutant RI-subunit was generated by oligonucleotide-directed muta-genesis and lacks the entire second cAMP-binding domain which includes both of the residues, Trp260 and Tyr371, that are photolabeled in the native RI-subunit. The mutant RI-subunit, nevertheless, is photoaffinity-labeled with high efficiency, and the residue covalently modified was identified as Tyr244. The position of Tyr244 based on a computer graphic model of cAMP-binding site A is proposed and correlated with the presumed locations of Tyr371 and Trp260 in the native R-subunit. Photoaffinity labeling also can be used to detect functional cAMP-binding sites following electrophoretic transfer of the denatured protein to nitrocellulose. Labeling of the immobilized protein on nitrocellulose required a functional cAMP-binding site A that can be photoaffinity-labeled in solution based on the following criteria. 1) The type I R-subunit is photolabeled, whereas the type II R-subunit is not. A primary feature which distinguishes these two R-subunits is that the RI-subunit is photolabeled at both sites A and B, whereas covalent modification of the RII-subunit occurs only at site B. 2) The truncated mutant of the RI-subunit which lacks the entire second cAMP-binding domain can be photolabeled on nitrocellulose. 3) A mutant RI-subunit which can no longer be photolabeled in site B is still photolabeled on nitrocellulose. 4) A mutation which abolished cAMP binding to site A also abolished photoaffinity labeling after transfer to nitrocellulose.

Affinity Labels↗

PubMed1987

Distribution of cAMP and cAMP-dependent protein kinases in Aplysia sensory neurons.

Sensitization of the gill- and siphon-withdrawal reflex in Aplysia is considered a simple form of learning. Previous work has provided physiological and pharmacological evidence that cAMP-dependent protein phosphorylation within identified sensory neurons of the abdominal ganglion underlies the short-term form of this behavioral modification. Our main goal in this paper is to determine the subcellular distribution of cAMP and to measure the amounts and properties of the 2 types of subunits (regulatory and catalytic) that constitute the cAMP-dependent protein kinase. Do these biochemical parameters differ in sensory cells from those in other parts of nervous tissue? We found that the increased cAMP synthesized under conditions of sensitization is distributed in 3 compartments in the neuron: most of it is free in the cytoplasm; the remainder is bound either to cytoplasmic or to particulate proteins, which are believed to be regulatory subunits of the cAMP-dependent protein kinase. Binding of cAMP within the neurons is a measure of activation of the kinase. At rest, 17% of the binding sites in sensory cells were occupied. After brief electrical stimulation of the connective, which released endogenous transmitter, occupancy increased to 34%. This treatment increased the amount of cAMP bound to the various binding proteins differentially. The biochemical characteristics of cAMP binding were found to be the same in sensory neurons as in the rest of the nervous system but different from those in muscle. Thus, memory and learning are likely to be mediated by enzymes that are shared by other nerve cells. We found that sensory neurons have greater cAMP-dependent protein kinase activity than other neurons, however, and as a result may be more sensitive to small increases of cAMP.

Animals↗

PubMed1982

Effect of cAMP phosphodiesterase inhibitors on ADP-induced shape change, cAMP and nucleoside diphosphokinase activity of rabbit platelets.

The effects of cAMP phosphodiesterase inhibitors on ADP-induced shape change and cAMP concentrations have been studied. Caffeine (10 mM), theophylline (8 mM), dipyridamole (0.2 mM), or papaverine (0,05 mM) prevented the shape change of washed rabbit platelets induced by 0.4 microM ADP. At these concentrations, none of these cAMP phosphodiesterase inhibitors increased 14C-cAMP in platelets in which the cytoplasmic adenine nucleotides had been labelled with 14C-adenine. By a protein binding assay, only papaverine by itself increased platelet cAMP above its basal level. These results indicate that two pools of cAMP may exist in platelets. Both methods showed that stimulation of platelet adenylate cyclase with PGE1 (1 microM) resulted in an increase in platelet cAMP and all these cAMP phosphodiesterase inhibitors potentiated this increase caused by PGE1. By themselves, some of these compounds may act through mechanisms that do not involve platelet cAMP. The effects of these cAMP phosphodiesterase inhibitors on platelet nucleoside diphosphokinase (NDK) activity were also investigated. At concentrations that prevented ADP-induced shape change, papaverine and dipyridamole had no effect on the formation of 14C-ATP from 14C-ADP by washed rabbit platelets. The methylxanthines partially inhibited NDK activity of washed rabbit platelets and of isolated platelet membranes, probably due to the structural similarity between the adenine ring of ADP and these substances. However, adenine (8 mM) inhibited ADP-induced shape change and platelet NDK activity but was a less effective inhibitor of ADP-induced platelet aggregation. Thus it seems unlikely that interference with platelet NDK or the ADP receptor is the major mechanism by which the methylxanthines inhibit platelet functions.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1993

Reciprocal regulation of mRNA and protein for subunits of cAMP-dependent protein kinase (RI alpha and C alpha) by cAMP in a neoplastic B cell line (Reh).

The present study examines the activity, levels of expression and regulation of cAMP-dependent protein kinase subunits during cAMP-mediated inhibition of Reh cell proliferation. Human Reh cells express mRNAs for the RI alpha and C alpha subunits of cAK at high levels and are practically devoid of cAMP-dependent protein kinase type II. Treatment with isoproterenol, forskolin, or a cAMP analog increased RI alpha mRNA in a time- and concentration-dependent manner (maximal, 4-fold, at 4-8 h). Messenger RNA for C alpha was also stimulated by cAMP, although with slower kinetics (maximal, 2-fold, at 16-24 h). Nuclear run-on assays showed a 2-fold increase in RI alpha gene transcription, whereas that of C alpha was unchanged. In spite of the stimulatory effects of cAMP on mRNAs for both RI alpha and C alpha, phosphotransferase activity and specific [3H]cAMP binding decreased rapidly after treatment with either cAMP or forskolin. Interestingly, the decrease in R and C activity preceded the increase in RI alpha and C alpha mRNA levels, raising the question whether increased mRNA levels may be secondary to the decrease in RI alpha or C alpha protein. The finding that the protein synthesis inhibitor cycloheximide gave changes in RI alpha and C alpha mRNA similar to cAMP and that co-treatment with cycloheximide and cAMP resulted in additive effects tend to support this notion.

Adenylyl Cyclases↗

PubMedDate not supplied

Camp nursing: can children with asthma safely attend a regular outdoor day camp?

Although specialty camps are available nationwide for children with asthma, many families prefer to have their children attend regular camps. A retrospective descriptive study was undertaken to evaluate the needs of 156 children, ages 3-16 years, with asthma who attended a large, outdoor, nonspecialty, day camp in a suburban wooded setting. Findings indicate that 10.9% (n = 17) received scheduled daily asthma medication, and 12.2% (n = 19) required PRN asthma medication while attending camp. Twenty-one children (13.5%) presented, at least once, to the camp nursing office with respiratory complaints. Of a total of 35 visits to the camp nursing office for acute asthma problems, 20% (n = 7) required the child to leave camp. Nurses can encourage parents to learn about camp facilities and policies to enable them to carefully evaluate safety when considering a camp for their child with asthma.

Adolescent↗

PubMed1991

[Purification and characterization of cAMP-dependent protein kinases of yeasts in a Saccharomyces cerevisiae wild strain and selected mutants of cAMP metabolism].

Protein kinases represent a diverse family of enzymes that play a critical role in regulation. Among nearly 100 known protein kinases, the cAMP-dependent enzyme is best understood biochemically. Unlike other protein kinases, cAMP-dependent protein kinase consists of two different types of subunits that dissociate, a regulatory subunit (R), which is the receptor for cAMP, and a catalytic subunit (C). In the absence of cAMP, the enzyme exists as an inactive tetramer, R2C2. The binding of intracellular cAMP to the R subunit decreases the affinity of the R subunit for the C subunit by approximately four orders of magnitude and, under physiological conditions, leads to dissociation of the holoenzyme into R2(cAMP)4 dimer and two free C subunits that are catalytically active. Mutants of the cAMP metabolism, adenylate cyclase and cell cycle mutants, provided further information about protein synthesis and cellular growth in Saccharomyces cerevisiae. The purified protein kinases were divided into different types according to their elution profiles from the DEAE-cellulose matrix. Two types of cAMP-dependent and two types of cAMP-independent protein kinases were isolated from the wild strain. Differences in the activities of the kinases in the mutants showed a close relationship to the locus of the respective mutations in the cell-cycle. Some properties of the protein kinases are discussed with respect to individual mutations.

Adenylyl Cyclases↗

PubMed2003

cAMP-dependent protein kinase and reward-related learning: intra-accumbens Rp-cAMPS blocks amphetamine-produced place conditioning in rats.

RATIONALE: Dopamine may produce reward-related learning by activating D(1)-like receptors in the nucleus accumbens (NAc) and stimulating the formation of cyclic adenosine monophosphate (cAMP) and the activation of cAMP-dependent protein kinase (PKA). OBJECTIVES: This hypothesis was tested using the conditioned place preference (CPP) based on NAc injections of amphetamine (amph) and evaluating the effects of PKA inhibition with Rp-cAMPS. METHODS: The CPP procedure consisted of three phases: pre-exposure (three 15-min sessions in a chamber consisting of two distinct compartments connected by a tunnel), conditioning (four 30-min placements into one compartment with the tunnel blocked following drug injection into the NAc alternating with four similar placements into the other side following NAc injection of saline), and test (one 15-min session with the tunnel open). A CPP was defined as an increase in time spent on the drug-paired side from mean pre-exposure to test. RESULTS: Dose-response experiments showed that 15.0 or 20.0 but not 5.0 or 10.0 micro g/0.5 micro l per side of amph produced a CPP. The amph (20.0 micro g) CPP was blocked by Rp-cAMPS co-injections of 25.0 and 250 but not 2.5 ng/0.5 micro l per side. Rp-cAMPS or the PKA activator Sp-cAMPS (50.0, 250, 500, 600 ng/0.5 micro l per side) alone had no effect on side preference. Co-injection of 10.0 micro g amph+Sp-cAMPS (25.0, 50.0, 250, 500 ng) did not result in a CPP but co-injection of 20.0 micro g amph+Sp-cAMPS (250 ng) led to a loss of the CPP normally seen with that dose of amph. Doses of Rp-cAMPS that blocked CPP did not block the locomotor stimulatory effect of amph during conditioning sessions. CONCLUSIONS: Results supported the hypothesis that PKA activation in NAc is necessary for reward-related learning.

Amphetamine↗

PubMed1992

Effect of some new cAMP analogs on cAMP-dependent protein kinase isoenzymes.

1. Ten new cAMP analogs were synthesized by replacing the purine ring with with indazole, benzimidazole or benztriazole and/or their nitro and amino derivatives. 2. Each analog proved effective in activating cAMP-dependent protein kinase I (PK-I) purified from rabbit skeletal muscle and cAMP-dependent protein kinase II (PK-II) from bovine heart and chasing 8-[3H]cAMP bound to regulatory subunits in the half-maximal effective concentrations of 2 x 10(-8)-8 x 10(-6) M. 3. The N-1-beta-D-ribofuranosyl-indazole-3'5'-cyclophosphate(I) proved a very poor chaser and activator of both isoenzymes, but when indazole was attached at its N-2 to ribose (IV) or when its H at C-4 (equivalent to the position of amino-group in adenine) was substituted by an amino-(III) or especially nitro-group (II) its efficiency was dramatically increased. 4. Analogs containing benztriazole ring proved as powerful as cAMP irrespective of the presence of substituents (VII-X). 5. Benzimidazole derivatives with amino-(VI) or nitro-group (V) activated PK-II 3 and 20 times better than PK-I. 6. Attaching of ribose to N-2 of indazole or benztriazole increased the affinity to PK-II 10 and 4 times, respectively. 7. Chasing efficiency of cAMP analogs at half-saturating [3H]cAMP tended to correlate with activating potency only for PK-I but at saturating [3H]cAMP concentration for both isoenzymes. 8. On the basis of synergistic activation with 8-Br-cAMP a site 2-selective binding of nitro-benzimidazole (V) and unsubstituted benztriazole (VII) derivatives to PK-II is suggested.

Cyclic AMP↗