PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 15356187

Adenosine postsynaptically modulates supraoptic neuronal excitability.

Todd A Ponzio·Glenn I Hatton
View original source ↗Export metadata ↓

Abstract

Effects of adenosine on the excitability of supraoptic nucleus neurons were investigated in whole cell patch-clamp experiments conducted in horizontal slices of rat hypothalamus. Adenosine (10-100 muM) inhibited all neurons tested by reducing or abolishing spontaneous or evoked discharge. Large hyperpolarizations were seen, averaging -6.08 +/- 0.83 mV below resting membrane potential, and action potential durations were significantly reduced by 134 +/- 41 mus in the presence of 100 muM adenosine. The A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1 muM) blocked these effects, whereas the A(1) agonists N(6)-cyclopentyladenosine (CPA) and N(6)-cyclohexyladenosine (CHA) mimicked the actions of adenosine. A(2) receptor contributions to excitability were assessed by application of an A(2) agonist, carboxamidoadenosine (CPCA). This resulted in membrane depolarizations (3.56 +/- 0.65 mV) and maintenance of firing. The presence of endogenous adenosine in the slice was revealed by both the application of the adenosine uptake inhibitor dilazep (1-100 muM), which resulted in a strong inhibition of firing activity, and the application of DPCPX, which induced firing in cells silenced by negative current injection. We tested for postsynaptic actions of adenosine by blocking G protein activation via GDP-beta-S infusion into recorded neurons. Under these conditions, the adenosinergic inhibition of firing and reduction of spike duration were blocked, suggesting the effects were mediated by postsynaptic adenosine receptors. That the effects on excitability could be due to direct activation of adenosine A(1) receptors on supraoptic neurons was further explored immunocytochemically via the co-labeling of magnocellular neurons with polyclonal antibodies raised against the A(1) receptors. It is concluded that adenosine, acting at postsynaptic A(1) receptors, exhibits a powerful inhibitory influence on supraoptic magnocellular activity and is an important endogenous regulator of magnocellular neuroendocrine function.

Explore related subjects

AdenosineAnalgesicsAnimalsCalciumDose-Response Relationship, DrugDrug InteractionsHydroxyprolineImmunohistochemistryIn Vitro TechniquesMaleMembrane PotentialsNeural InhibitionNeuronsPatch-Clamp TechniquesPurinergic P1 Receptor AgonistsPurinergic P1 Receptor AntagonistsRatsRats, Sprague-DawleyReceptors, Purinergic P1Supraoptic NucleusSynapsesSynaptic TransmissionXanthinesComparative StudyJournal ArticleResearch Support, U.S. Gov't, P.H.S.

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Todd A Ponzio, Glenn I Hatton. 2004-09-08. Adenosine postsynaptically modulates supraoptic neuronal excitability.. https://doi.org/10.1152/jn.01185.2003

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Solution structure of domain 6 from a self-splicing group II intron ribozyme: a Mg(2+) binding site is located close to the stacked branch adenosine.

Group II intron self-splicing is essential for the correct expression of organellar genes in plants, fungi, and yeast, as well as of bacterial genes. Self-excision of these autocatalytic introns from the primary RNA transcript is achieved in a two-step mechanism that is apparently analogous to that of the eukaryotic spliceosome. The 2'-OH of a conserved adenosine (the branch point) located within domain 6 (D6) acts as the nucleophile in the first step of splicing. Despite the biological importance of group II introns, little is known about their structural organization and usage of metal ions in catalysis. Here we report the first solution structure of a catalytically active D6 construct encompassing the branch point and the neighboring helical regions from the mitochondrial yeast intron ai5gamma. The branch adenosine is the single unpaired nucleotide, and, in contrast to the spliceosomal branch site, resides within the helix, being partially stacked between two flanking GU wobble pairs. We identified a novel prominent Mg(2+) binding site in the major groove of the branch site. Importantly, Mg(2+) addition does not impair the stacking of the branch adenosine, rather it strengthens the interaction with the flanking uridines, as shown by NMR and fluorescence studies. This means that domain 6 presents the branch adenosine in a stacked fashion to the core of group II introns upon folding to the active conformation.

Adenosine↗
PubMed2007

Synthesis and biological evaluation of novel 1-deoxy-1-[6-[((hetero)arylcarbonyl)hydrazino]- 9H-purin-9-yl]-N-ethyl-beta-D-ribofuranuronamide derivatives as useful templates for the development of A2B adenosine receptor agonists.

The lack of molecules endowed with selective and potent agonistic activity toward the hA2B adenosine receptors has limited the studies on this pharmacological target and consequently the evaluation of its therapeutic potential. We report the design and the synthesis of the first potent (EC50 in the nanomolar range) and selective hA2B adenosine receptor agonists consisting of 1-deoxy-1-[6-[((hetero)arylcarbonyl)hydrazino]-9H-purin-9-yl]-N-ethyl-beta-D-ribofuranuronamide derivatives. The concurrent effect of 6-substitution of the purine nucleus with a ((hetero)arylcarbonyl)hydrazino function and a 2-chloro substitution has been investigated in such NECA derivatives.

Adenosine↗
PubMed2007

Enhanced CXCL1 production and angiogenesis in adenosine-mediated lung disease.

Angiogenesis is a feature of chronic lung diseases such as asthma and pulmonary fibrosis; however, the pathways controlling pathological angiogenesis during lung disease are not completely understood. Adenosine is a signaling molecule that has been implicated in the exacerbation of chronic lung disease and in the regulation of angiogenesis; however, the relationship between these factors has not been investigated. The current study utilized adenosine deaminase (ADA)-deficient mice to determine whether chronic elevations in adenosine in vivo result in pulmonary angiogenesis. Results demonstrate substantial angiogenesis in the tracheas of ADA-deficient mice in association with adenosine elevations. ADA replacement enzyme therapy resulted in a lowering of adenosine levels and reversal of tracheal angiogenesis, indicating that the increases in vessel number are dependent on adenosine elevations. Levels of the angiogenic chemokine CXCL1 (mouse functional homologue of human IL-8) were found to be elevated in an adenosine-dependent manner in the lungs of ADA-deficient mice. Neutralization of CXCL1 and its receptor, CXCR2, resulted in the inhibition of angiogenic activity, which suggests that CXCL1 signaling through the CXCR2 receptor mediated the observed increases in angiogenesis. Our findings suggest that adenosine plays an important role, via CXCL1, in the induction of pulmonary angiogenesis.

Adenosine↗