Vasoactive intestinal peptide regulates extracellular adenosine levels in rat cortical cultures. 1995

P A Rosenberg, and Y Li
Department of Neurology and Program in Neuroscience, Children's Hospital, Boston, MA 021115, USA. rosenberg@al.tch.harvard.edu

Adenosine is an important inhibitory neuromodulator in the cerebral cortex, yet it remains unclear how extracellular adenosine concentrations are regulated. Recently, it has been shown that beta-adrenergic receptor stimulation in rat cortical cultures causes the accumulation of extracellular adenosine derived by enzymatic hydrolysis from adenosine cyclic monophosphate (cAMP) transported into the extracellular space. In this study we show that vasoactive intestinal peptide (VIP), in addition to activating adenylyl cyclase and promoting the accumulation of intracellular cAMP in rat cortical cultures, also causes transport of cAMP and accumulation of extracellular adenosine. We further show that the extracellular accumulation of adenosine in response to VIP can be blocked by inhibition of cAMP transport, cyclic nucleotide phosphodiesterase activity, and 5'-nucleotidase, indicating that extracellular cAMP is the source of the adenosine. Cyclic AMP transport may be a general mechanism by which a variety of neuromodulators that act upon receptors coupled to adenylyl cyclase might regulate extracellular adenosine levels and thereby inhibitory tone in the cerebral cortex.

UI MeSH Term Description Entries
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
D009479 Neuropeptides Peptides released by NEURONS as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. Neuropeptide
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
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
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
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
D005110 Extracellular Space Interstitial space between cells, occupied by INTERSTITIAL FLUID as well as amorphous and fibrous substances. For organisms with a CELL WALL, the extracellular space includes everything outside of the CELL MEMBRANE including the PERIPLASM and the cell wall. Intercellular Space,Extracellular Spaces,Intercellular Spaces,Space, Extracellular,Space, Intercellular,Spaces, Extracellular,Spaces, Intercellular
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
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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