Biomaterial Database

Effects of acute and chronic ethanol on cyclic AMP accumulation in NG108-15 cells: differential dependence of changes on extracellular adenosine. 1995

E Kelly, and P K Harrison, and R J Williams

Department of Pharmacology, School of Medical Sciences, University of Bristol.

1. This study investigated the effects of acute and chronic ethanol on basal, agonist- and forskolin-stimulated cyclic AMP formation in NG108-15 mouse neuroblastoma x rat glioma hybrid cells, and examined the role of changes in extracellular adenosine concentrations on the effects observed. 2. NG108-15 cells incubated acutely with ethanol (1-200 mM) displayed concentration-dependent increases in basal and iloprost-stimulated (300 nM; a prostanoid IP receptor agonist) cyclic AMP accumulation but a concentration-dependent decrease in forskolin-stimulated (10 microM) accumulation. 3. Cells treated chronically with ethanol (200 mM) for 48 h displayed increases over control in basal, iloprost- (0.001-10 microM) and forskolin (0.01-100 microM)-stimulated cyclic AMP formation. However, chronic ethanol did not affect [3H]-iloprost binding to cell membranes. 4. Inclusion of adenosine deaminase (ADA; 1 unit ml-1) during the incubation period to measure cyclic AMP accumulation completely abolished the increase in basal accumulation following chronic ethanol, but did not affect the increase in iloprost stimulation. On the other hand ADA partially reversed the increase in forskolin stimulation following chronic ethanol, but even in the presence of high concentrations of ADA (5 units ml-1) the forskolin stimulation remained elevated above control. 5. Cells treated chronically with the adenosine receptor agonist 5'-(N-ethylcarboxamido)-adenosine (NECA; 10 microM for 48 h) displayed a reduction in subsequent NECA- and forskolin-stimulated cyclic AMP accumulation, but iloprost stimulation was not affected. ADA included acutely during the incubation period to measure cyclic AMP accumulation abolished the reduction in forskolin but not NECA stimulation produced by the chronic NECA pretreatment. 6. We have previously noted that ethanol inhibits NG108-15 cell proliferation and alters cell morphology.To mimic this, cells were incubated in the absence of foetal calf serum for 48 h. Following this time, basal, iloprost- and forskolin-stimulated cyclic AMP formation was enhanced over that in cells grown in the presence of serum.7. These results indicate that chronic ethanol enhances cyclic AMP formation in intact NG108-15 cells by more than one mechanism: one involves increased extracellular adenosine concentrations and the other a change in the transduction system beyond the receptor, possibly involving the adenylyl cyclase enzyme. Furthermore the ethanol-induced changes in cyclic AMP accumulation may relate to alterations in NG108-15 cell growth and development.

UI	MeSH Term	Description	Entries
D009447	Neuroblastoma	A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)	Neuroblastomas
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005576	Colforsin	Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.	Coleonol,Forskolin,N,N-Dimethyl-beta-alanine-5-(acetyloxy)-3-ethenyldodecahydro-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-1H-naphtho(2,1-b)pyran-6-yl Ester HCl,NKH 477,NKH-477,NKH477
D000241	Adenosine	A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.	Adenocard,Adenoscan
D000242	Cyclic AMP	An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.	Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000243	Adenosine Deaminase	An enzyme that catalyzes the hydrolysis of ADENOSINE to INOSINE with the elimination of AMMONIA.	Adenosine Aminohydrolase,Aminohydrolase, Adenosine,Deaminase, Adenosine
D000431	Ethanol	A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.	Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014407	Tumor Cells, Cultured	Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.	Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D016285	Iloprost	An eicosanoid, derived from the cyclooxygenase pathway of arachidonic acid metabolism. It is a stable and synthetic analog of EPOPROSTENOL, but with a longer half-life than the parent compound. Its actions are similar to prostacyclin. Iloprost produces vasodilation and inhibits platelet aggregation.	Ciloprost,Ventavis,ZK-36374,ZK 36374,ZK36374