Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stimulation of cyclic AMP (cAMP) accumulation in rat cortex slices by 1 microM forskolin (F) was markedly reduced (96%) by treatment with adenosine deaminase (ADA). The effect of ADA was progressively less at higher concentrations of F, but still inhibited the response by 50% at 100 microM F. ADA-mediated inhibition of the cAMP response to 1 microM F was completely reversed by 5 microM 2-chloroadenosine (CA), an ADA-resistant analogue. Stimulation by F (controls) and F plus CA (ADA treated) in cortex slices was significantly inhibited by 200 microM caffeine (CAF) and by 10 microM 8-phenyltheophylline. cAMP accumulation in ADA-treated cortex slices stimulated with CA at concentrations from 5 to 100 microM was markedly enhanced by 1 microM F. Neither ADA treatment nor 200 microM CAF significantly affected cAMP accumulation in slices stimulated by 1 microM vasoactive intestinal polypeptide or adenylate cyclase in membranes stimulated by 1 microM F. CAF (1 mM) did not significantly increase basal cAMP levels in cortex slices, whereas 1 mM 3-isobutyl-1-methylxanthine caused a significant 80% increase and 100 microM rolipram enhanced cAMP levels by 4.5-fold. F-stimulated cAMP accumulation (1 microM) in cortex slices was inhibited 98% by 1 mM CAF and 49% by 1 mM 3-isobutyl-1-methylxanthine, and was enhanced 2.5-fold by 100 microM rolipram. These data have been interpreted to indicate that the stimulation of cAMP accumulation in rat cortex slices by 1 microM F is predominantly due to synergistic interaction with endogenous adenosine and that the inhibition of this response by CAF is largely due to blockade of adenosine receptors.
...
PMID:Forskolin stimulation of cyclic AMP accumulation in rat brain cortex slices is markedly enhanced by endogenous adenosine. 130 35

Neuropeptide Y (NPY) receptors in the SK-N-MC human neuroblastoma cell line couple to mobilization of intracellular Ca2+ and inhibition of adenylylcyclase. Pretreatment of SK-N-MC cells with isoproterenol enhanced the NPY-stimulated Ca2+ mobilization, mainly by increasing the maximal response to NPY. The enhancement was time-(maximal after 24 h) and concentration-dependent (maximal at 10 microM isoproterenol), blocked by the beta-adrenergic antagonist propranolol, and mimicked by forskolin. Concomitant treatment with cycloheximide prevented the enhancing effect of isoproterenol, suggesting the involvement of protein synthesis. Isoproterenol treatment did not alter the number or affinity of 125I-labeled NPY binding sites, the amount of pertussis toxin substrates, or NPY-mediated inhibition of cAMP accumulation. Similarly, isoproterenol treatment had no effect on basal intracellular Ca2+ and on Ca2+ increases elicited by carbachol, caffeine, or ionomycin. We conclude that isoproterenol treatment can sensitize NPY receptor responsiveness in a way that is specific for Ca2+ mobilization mechanisms used by this hormone.
...
PMID:NPY-stimulated Ca2+ mobilization in SK-N-MC cells is enhanced after isoproterenol treatment. 131 94

Trabeculae from the right ventricle of rat were chemically 'skinned' with saponin (50 micrograms ml-1 for 30 min). Caffeine (10 mM) induced a transient contracture as a consequence of Ca(2+)-release from the sarcoplasmic reticulum and subsequent activation of the myofilaments. The amplitude of the caffeine contracture was used as an index of the Ca(2+)-content of the sarcoplasmic reticulum. cAMP (0.1-10 microM) markedly potentiated the caffeine-induced response under standardized conditions. This was interpreted as a cAMP-induced increase in Ca2+ accumulation by the sarcoplasmic reticulum during the Ca2+ loading period before the application of caffeine. After removal of cAMP, the amplitude of the regularly evoked contractures slowly declined towards standard levels. The characteristic effects of cAMP on the caffeine contracture were mimicked by addition of forskolin (10(-6) M), a substance known to stimulate cAMP production by adenylate cyclase. The results suggest that a significant quantity of functional adenylate cyclase persists after saponin treatment. In these preparations cAMP had no effect on the apparent Ca(2+)-sensitivity of the myofilaments. If the preparations were exposed briefly to saponin, cAMP caused a decrease in the apparent Ca2+ sensitivity of the contractile proteins. However, further exposure to saponin, or to Triton X-100, caused a marked increase in maximum Ca(2+)-activated force (Cmax). It was concluded that 'briefly' saponin-treated preparations, exhibiting a reduction in Ca2+ sensitivity in response to cAMP, are not uniformly permeable to the bathing solution.
...
PMID:Effects of cAMP and forskolin on caffeine-induced contractures and myofilament Ca-sensitivity in saponin-treated rat ventricular trabeculae. 131 80

In view of the possible association between ingestion of caffeine (a constituent of coffee, tea, and several beverages) and osteoporosis, we have studied the effect of caffeine on bone resorption in vitro. Caffeine caused a dose-dependent increase of the spontaneous release of 45Ca from neonatal mouse calvarial bones. The effect of caffeine was less pronounced than that of parathyroid hormone (PTH), but of the same magnitude as that of theophylline, a structurally related methylxanthine. The enhancement of 45Ca release induced by caffeine and PTH was observed in 5 days culture. In 2 days culture, however, only PTH stimulated mineral mobilization. The delayed stimulatory effect of caffeine in long-term cultures was abolished by indomethacin and flurbiprofen. In indomethacin-treated bones, however, caffeine potentiated the stimulatory effect on 45Ca release induced by choleratoxin and forskolin. In contrast, caffeine did not potentiate 45Ca release stimulated by PTH. These data show that caffeine can stimulate calcium release from bone in vitro and that this effect is due to potentiation of a stimulatory action of a bone resorptive agonist acting via the adenylate cyclase-cyclic AMP system.
...
PMID:Caffeine has the capacity to stimulate calcium release in organ culture of neonatal mouse calvaria. 145 Oct 9

Recent experimental data indicate a probable role of adenosine as an endogenous neuroprotective substance in brain ischemia. This nucleoside is rapidly formed during ischemia as a result of intracellular breakdown of ATP and it is subsequently transported into the extracellular space. With use of microdialysis and other techniques, a massive increase of interstitial adenosine has been measured during ischemia in different brain areas. Adenosine acts through two subtypes of receptors, A1 and A2, which are located on neurons, glial cells, blood vessels, platelets, and leukocytes and are linked via G-proteins to different effector systems such as adenylate cyclase and membrane ion channels. There is a very high density of A1-receptors in the hippocampus, an area with specific vulnerability to ischemia. In different in vivo and in vitro models of brain ischemia, the pharmacological manipulation of the adenosine system by adenosine receptor antagonists tended to aggravate ischemic brain damage, whereas the reinforcement of adenosine action by receptor agonists or inhibitors of cellular reuptake and inactivation showed neuroprotection. The up-regulation of adenosine A1-receptor number and affinity by chronic preadministration of the competitive antagonist caffeine also attenuated ischemic brain damage. The mechanisms underlying the neuroprotective effects of adenosine seem to involve both types of adenosine receptors, A1 and A2, but the A1-mediated pre- and postsynaptic neuromodulation may be of special importance. By inhibiting neuronal Ca2+ influx, adenosine counteracts the presynaptic release of the potentially excitotoxic neurotransmitters glutamate and aspartate, which may impair intracellular Ca2+ homeostasis via metabotrophic glutamate receptors or induce uncontrolled membrane depolarization via ion channel-linked glutamate receptors, especially of the N-methyl-D-aspartate (NMDA) type. In addition, adenosine directly stabilizes the neuronal membrane potential by increasing the conductance for K+ and Cl- ions, thereby counteracting excessive membrane depolarization. The latter triggers a number of pathological events including blockade of voltage-sensitive K+ currents, increase of NMDA receptor-mediated Ca2+ influx, and presumably also impairment of glutamate uptake by astrocytes. In the way of a vicious cycle, all these factors again tend to enhance extracellular glutamate levels and membrane depolarization, finally leading to cytotoxic calcium loading and neuronal cell death. In addition to its important neuromodulatory effects, which tend to reduce energy demand of the brain, adenosine acting via A2-receptors in brain vessels, platelets, and neutrophilic granulocytes may improve the cerebral microcirculation and thus oxygen and substrate supply to the tissue. There is evidence that the functional state of adenosine receptors is impaired during ischemia, limiting the time window of the adenosine action.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Adenosine and brain ischemia. 148 19

1. The intracellular mechanism of heterosynaptic facilitation (HSF) formation in identified neurons from the snail Planorbis corneus has been studied. 2. Facilitation of excitatory postsynaptic currents (EPSC) were induced by (a) stimulation of pallial nerve, and (b) addition to extracellular saline of serotonin, NaF, papaverine, theophylline, caffeine or dibutril-cAMP. 3. A depression of EPSC in solutions containing tolbutamide, a cAMP-dependent protein kinase inhibitor was observed. 4. In some cases the similar facilitation or depression of the current induced by acetylcholine application (ACh-current) was found in the same neuron. 5. The effects on ACh-current were distorted in solutions containing caffeine, a well-known activator of calcium ions release from the intracellular depot. 6. According to our findings, we suggest that adenylate cyclase activity of postsynaptic cells could underlie the formation of HSF and it is likely that this activity was modulated by intracellular concentration of calcium ions.
...
PMID:Analysis of heterosynaptic facilitation in identified giant neurons from cerebral ganglion of the pond snail Planorbis corneus. 167 48

1. Octopamine (OA) (10(-7)-10(-5) M) relaxed isolated foreguts. Tyramine mimicked the effects of OA but was 64x less potent. 2. Proctolin (10(-8) M to 10(-6) M) induced contraction of isolated foreguts was antagonised non competitively by tyramine. 3. Mianserin (10(-6) M) was a non competitive antagonist of relaxation caused by tyramine but was without effect on proctolin induced contraction. 4. Caffeine (1 microM and 2 microM) caused non competitive inhibition of proctolin-induced tissue contraction. 5. It is concluded that tyramine antagonises proctolin-induced contraction of the foregut by activating an adenylate cyclase-linked OA2 receptor.
...
PMID:Tyramine antagonizes proctolin-induced contraction of the isolated foregut of the locust Schistocerca gregaria by an interaction with octopamine2 receptors. 197 52

We tested the hypothesis that the adenylate cyclase system and Na+, K(+)-ATPase are reciprocally related in rat pancreatic islets. We studied the effect of theophylline, caffeine, and dibutyryl cyclic AMP on Na+, K(+)-ATPase activity in a membrane preparation from collagenase-isolated rat islets. Theophylline, caffeine, or dibutyryl cyclic AMP, in concentrations of 1 mM, all inhibited Na+, K(+)-ATPase activity (44,62, and 43%, respectively). Kinetic analysis indicated that theophylline and dibutyryl cAMP inhibit Na+, K(+)-ATPase by different mechanisms; theophylline decreased Vmax and decreased apparent Km (ATP), whereas dibutyryl cAMP decreased Vmax and increased apparent Km (ATP). Similar inhibition of Na+, K(+)-ATPase by theophylline or dibutyryl cAMP was noted in a particulate fraction from rat kidney and in a purified porcine brain Na+, K(+)-ATPase preparation. The adenylate cyclase system and Na+, K(+)-ATPase may act reciprocally in pancreatic islets and in other tissues. In the beta cell this relationship may be essential in coordinating consumption of ATP in the stimulated, as opposed to the rest, state.
...
PMID:Relationships between adenylate cyclase and Na+, K(+)-ATPase in rat pancreatic islets. 215 93

We examined expression of the Dictyostelium cAMP phosphodiesterase (PDE) gene under conditions that alter intracellular cAMP levels during in vitro differentiation of wild-type strain V12M2 and a sporogenous derivative, HB200. In control cultures, cellular PDE activity peaked at 6 hr and declined by 8 hr, while secreted PDE activity continued to increase through 8 hr. Lowering intracellular cAMP levels with caffeine or progesterone increased cellular and secreted PDE activities 2-fold, increased stalk cell differentiation, and inhibited spore differentiation. In contrast, exposure to 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP; a membrane-permeable cAMP analog) or ammonia (which promotes intracellular cAMP accumulation in V12M2 and HB200 cells) lowered PDE activities by as much as 45%, decreased stalk cell differentiation, and increased spore differentiation. Simultaneous exposure to 8-Br-cAMP and caffeine gave intermediate PDE activities as would be expected if 8-Br-cAMP entered the cell and bypassed the caffeine-mediated block to adenylate cyclase activation. In all cases, we observed commensurate changes in developmental PDE transcript levels. The developmental time course of expression was not significantly altered by these treatments. These results suggest that the magnitude of PDE gene expression is negatively regulated by intracellular cAMP levels and provide evidence for one of the earliest changes in gene expression that is consistent with cell-type specificity. These results are discussed in terms of a bistable switch employing intracellular cAMP as a regulator of cell fate.
...
PMID:Conditions that alter intracellular cAMP levels affect expression of the cAMP phosphodiesterase gene in Dictyostelium. 216 56

The EDTA-resistant cell-cell adhesion expressed at the aggregation stage of Dictyostelium discoideum is mediated by a cell surface glycoprotein of Mr 80,000 (gp80). The expression of gp80 is developmentally regulated by cyclic AMP (cAMP). In vitro nuclear run-on experiments show that transcription of the gp80 gene is initiated soon after the onset of development. The basal level of gp80 transcription is significantly augmented by exogenous cAMP pulses. Interestingly, in analog studies, 2'-deoxy-cAMP, 8-bromo-cAMP, and N6-monobutyryl-cAMP are all capable of inducing a rapid accumulation of gp80 mRNA, suggesting the presence of a unique cAMP receptor that responds equally well to these analogs. To determine whether intracellular cAMP plays a role in the regulation of gp80 expression, caffeine was used to block cAMP-induced receptor-mediated adenylate cyclase activation. Expression of gp80 mRNA was blocked in caffeine-treated cells but could be substantially restored by treatment with exogenous cAMP pulses, suggesting that adenylate cyclase activation is not required. gp80 expression was also examined in the signal transduction mutants synag 7 and frigid A. In both mutants, gp80 was expressed at the basal level. Pulses of cAMP as well as 2'-deoxy-cAMP and N6-monobutyryl-cAMP were capable of restoring the normal level of gp80 expression in synag 7 cells. These results, taken together, indicate bimodal regulation of gp80 expression during development and the involvement of a novel cAMP receptor in the transmembrane signalling pathway that regulates gp80 gene expression.
...
PMID:A pharmacologically distinct cyclic AMP receptor is responsible for the regulation of gp80 expression in Dictyostelium discoideum. 216 72


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---