8-Bromo-cAMP mimics beta-adrenergic sensitization of GABA responses to ethanol in cerebellar Purkinje neurons in vivo. 1996

R K Freund, and M R Palmer
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.

Previous studies in our laboratory indicated that electrophysiological responses of cerebellar Purkinje neurons to GABA were not routinely potentiated by ethanol (EtOH), and the potentiation was not large when it occurred. In the presence of beta-adrenergic agonists, such as isoproterenol, however, GABA inhibitions became sensitive to potentiation by EtOH in nearly every Purkinje neuron tested. beta-adrenergic receptor activation alone also modulates (potentiates) GABA responses on Purkinje neurons, and this has been reported to be mediated by a cAMP second messenger system. Herein, we report that the membrane-permeable cAMP analog, 8-bromoadenosine-3',5'-cyclic monophosphate (8-Br-cAMP), but not the membrane-impermeable cAMP, can also modulate GABA responses and that EtOH potentiates this facilitatory action of 8-Br-cAMP. These effects are not likely caused by adenosine receptor mechanisms, because this 8-bromoadenosine mediated modulation and sensitization was observed in the presence of systemic theophylline. These data suggest that the beta-adrenergic modulation and sensitization to EtOH of cerebellar Purkinje neuron GABA responses occur via a cAMP second messenger mechanism.

UI MeSH Term Description Entries
D008297 Male Males
D011689 Purkinje Cells The output neurons of the cerebellar cortex. Purkinje Cell,Purkinje Neuron,Purkyne Cell,Cell, Purkinje,Cell, Purkyne,Cells, Purkinje,Cells, Purkyne,Neuron, Purkinje,Neurons, Purkinje,Purkinje Neurons,Purkyne Cells
D011943 Receptors, Adrenergic, beta One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS. Adrenergic beta-Receptor,Adrenergic beta-Receptors,Receptors, beta-Adrenergic,beta Adrenergic Receptor,beta-Adrenergic Receptor,beta-Adrenergic Receptors,Receptor, Adrenergic, beta,Adrenergic Receptor, beta,Adrenergic beta Receptor,Adrenergic beta Receptors,Receptor, beta Adrenergic,Receptor, beta-Adrenergic,Receptors, beta Adrenergic,beta Adrenergic Receptors,beta-Receptor, Adrenergic,beta-Receptors, Adrenergic
D002531 Cerebellum The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills. Cerebella,Corpus Cerebelli,Parencephalon,Cerebellums,Parencephalons
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
D005680 gamma-Aminobutyric Acid The most common inhibitory neurotransmitter in the central nervous system. 4-Aminobutyric Acid,GABA,4-Aminobutanoic Acid,Aminalon,Aminalone,Gammalon,Lithium GABA,gamma-Aminobutyric Acid, Calcium Salt (2:1),gamma-Aminobutyric Acid, Hydrochloride,gamma-Aminobutyric Acid, Monolithium Salt,gamma-Aminobutyric Acid, Monosodium Salt,gamma-Aminobutyric Acid, Zinc Salt (2:1),4 Aminobutanoic Acid,4 Aminobutyric Acid,Acid, Hydrochloride gamma-Aminobutyric,GABA, Lithium,Hydrochloride gamma-Aminobutyric Acid,gamma Aminobutyric Acid,gamma Aminobutyric Acid, Hydrochloride,gamma Aminobutyric Acid, Monolithium Salt,gamma Aminobutyric Acid, Monosodium Salt
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
D015124 8-Bromo Cyclic Adenosine Monophosphate A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase. 8-Bromo-cAMP,8-Br Cyclic AMP,8-Bromo Cyclic AMP,8-Bromo Cyclic Adenosine Monophosphate, Monosodium Salt,8-Bromo Cyclic Adenosine Monophosphate, Sodium Salt,8-Bromoadenosine 3',5'-Cyclic Monophosphate,Br Cycl AMP,8 Br Cyclic AMP,8 Bromo Cyclic AMP,8 Bromo Cyclic Adenosine Monophosphate,8 Bromo Cyclic Adenosine Monophosphate, Monosodium Salt,8 Bromo Cyclic Adenosine Monophosphate, Sodium Salt,8 Bromo cAMP,8 Bromoadenosine 3',5' Cyclic Monophosphate,AMP, Br Cycl,Cyclic AMP, 8-Br,Cyclic AMP, 8-Bromo
D015290 Second Messenger Systems Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. Intracellular Second Messengers,Second Messengers,Intracellular Second Messenger,Messenger, Second,Messengers, Intracellular Second,Messengers, Second,Second Messenger,Second Messenger System,Second Messenger, Intracellular,Second Messengers, Intracellular,System, Second Messenger,Systems, Second Messenger

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