Effects of ethanol on basal and adenosine-induced increases in beta-endorphin release and intracellular cAMP levels in hypothalamic cells. 1999

N Boyadjieva, and D K Sarkar
Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA 99164-6520, USA.

Recently we have shown that the cAMP system is involved in ethanol-regulated beta-endorphin (beta-EP) release from rat hypothalamic neurons in primary cultures. The cascade of events that leads to activation of cAMP following ethanol treatment in hypothalamic beta-EP neurons is not apparent. In this study the role of adenosine, a cAMP regulator, in ethanol-regulated beta-EP release was determined by measuring the cellular incorporation of [3H]adenosine, intracellular cAMP levels and media immunoreactive (IR) beta-EP levels in cultures of rat hypothalamic cells following ethanol treatments in the presence and absence of an adenosine agonist and antagonist. Acute exposure to a 50 mM dose of ethanol for a period of 1 h increased media levels of IR-beta-EP and cellular contents of cAMP, but the ethanol treatment decreased [3H]adenosine uptake. Constant exposure to a 50 mM dose of ethanol for a period of 48 h, failed to alter media levels of IR-beta-EP, cell content of cAMP and [3H]adenosine uptake. The media level of IR-beta-EP was elevated following treatment with adenosine receptor agonist phenyl-isopropyl adenosine (PIA) and was reduced following treatment with adenosine receptor antagonist isobutylmethylxanthine (IBMX) or with adenosine uptake inhibitor adenosine deaminase. The level of cellular cAMP was also increased by PIA but was decreased by IBMX and adenosine deaminase. The stimulatory actions of the adenosine agonist PIA on IR-beta-EP release and on cAMP production were potentiated by simultaneous incubation with ethanol for 1 h. However, chronic ethanol exposure reduced PIA-induced IR-beta-EP release and cAMP production. Additionally, both IBMX and adenosine deaminase reduced ethanol-induced IR-beta-EP release and cAMP levels. These results suggest that ethanol inhibits adenosine uptake in IR-beta-EP neurons in the hypothalamus, thereby increasing extracellular levels of adenosine and leading to activation of membrane adenosine receptors, cAMP production and IR-beta-EP secretion from these neurons. Chronic ethanol desensitizes the adenosine-regulated cAMP production and IR-beta-EP release from hypothalamic neurons.

UI MeSH Term Description Entries
D007031 Hypothalamus Ventral part of the DIENCEPHALON extending from the region of the OPTIC CHIASM to the caudal border of the MAMMILLARY BODIES and forming the inferior and lateral walls of the THIRD VENTRICLE. Lamina Terminalis,Preoptico-Hypothalamic Area,Area, Preoptico-Hypothalamic,Areas, Preoptico-Hypothalamic,Preoptico Hypothalamic Area,Preoptico-Hypothalamic Areas
D007425 Intracellular Membranes Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES. Membranes, Intracellular,Intracellular Membrane,Membrane, Intracellular
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010660 Phenylisopropyladenosine N-Isopropyl-N-phenyl-adenosine. Antilipemic agent. Synonym: TH 162. Isopropylphenyladenosine,L-Phenylisopropyladenosine,N(6)-Phenylisopropyl-Adenosine,L Phenylisopropyladenosine
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
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
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

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