The 5-HT1 receptor agonist RU-24969 decreases 5-hydroxytryptamine (5-HT) release and metabolism in the rat frontal cortex in vitro and in vivo

Neocortical neurons in vivo are embedded in networks with intensive ongoing activity. How this network activity affects the neurons’ integrative properties and what function this may imply at the network level remain largely unknown. Most of our knowledge regarding synaptic communication and integration is based on recordings in vitro, where network activity is strongly diminished or even absent. Here, we present results from two complementary series of experiments based on intracellular in vivo recordings in anesthetized rat frontal cortex. Specifically, we measured 1) the relationship between the excursions of a neuron’s membrane potential and the spiking activity in the surrounding network and 2) how the summation of several inputs to a single neuron changes with the different levels of its membrane potential excursions and the associated states of network activity. The combination of these measurements enables us to assess how the level of network activity influences synaptic integration. We present direct evidence that integration of synaptic inputs in frontal cortex is linear, independent of the level of network activity. However, during periods of high network activity, the neurons’ response to synaptic input is markedly reduced in both amplitude and duration. This results in a drastic shortening of its window for temporal integration, requiring more precise coordination of presynaptic spike discharges to reliably drive the neuron to spike under conditions of high network activity. We conclude that ongoing activity, as present in the active brain, emphasizes the need for neuronal cooperation at the network level, and cannot be ignored in the exploration of cortical function.

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The Diameter of Retinal Arterioles Is Unaffected by Intravascular Administration of the Adenosine A2A Receptor Agonist Regadenoson in Normal Persons

Biomedicine Hub ◽

10.1159/000500563 ◽

2019 ◽

Vol 4 (2) ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Anna Dons-Jensen ◽

Line Petersen ◽

Hans-Erik Bøtker ◽

Toke Bek

Keyword(s):

Intravenous Administration ◽

Receptor Agonist ◽

Adenosine A2a Receptor ◽

Retinal Vessels ◽

Adenosine Receptor Agonists ◽

Retinal Arterioles ◽

A2a Receptor ◽

Adenosine A2a

Background: The neurotransmitter adenosine has been proposed to be involved in the pathogenesis of diabetic retinopathy, which may be due to the vasoactive properties of the compound. Previous studies have shown that adenosine can affect the tone of retinal arterioles in vitro to induce dilatation mediated by A2A and A2Breceptors and constriction mediated by A1 and A3 receptors. Purpose: To investigate effects of intravenous administration of the adenosine A2A receptor agonist regadenoson on the diameter of retinal vessels in vivo. Method: The diameter responses of larger retinal arterioles and venules were evaluated using the dynamic vessel analyser in 20 normal persons (age 22–31 years) after intravenous administration of the adenosine A2A receptor agonist regadenoson during exposure to systemic normoxia and hypoxia. Results: The diameter of retinal arterioles and venules increased significantly during stimulation with flickering light (p < 0.0001). Regadenoson reduced the flicker-induced dilatation of venules during normoxia (p = 0.0006), but otherwise had no effect on vessel diameters (p > 0.08 for all comparisons). Conclusions:Intravenous administration of the adenosine A2A receptor agonist regadenoson had no significant effect on the diameter of retinal arterioles. Future studies should investigate differential effects of intra- and extravascular administration of adenosine receptor agonists on retinal vessels.

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Effects of systemically administered ceruletide on dopamine metabolism in the rat frontal cortex: an in vivo microdialysis study

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)49606-6 ◽

1992 ◽

Vol 58 ◽

pp. 371

Author(s):

Yoko Hagino ◽

Takashi Moroji

Keyword(s):

Frontal Cortex ◽

In Vivo Microdialysis ◽

Dopamine Metabolism ◽

Microdialysis Study ◽

Rat Frontal Cortex

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Further pharmacological evaluation of a novel synthetic peptide bradykinin B2 receptor agonist

Biological Chemistry ◽

10.1515/hsz-2012-0295 ◽

2013 ◽

Vol 394 (3) ◽

pp. 353-360 ◽

Cited By ~ 9

Author(s):

Martin Savard ◽

Julie Labonté ◽

Céléna Dubuc ◽

Witold Neugebauer ◽

Pedro D’Orléans-Juste ◽

...

Keyword(s):

Knockout Mice ◽

Synthetic Peptide ◽

Receptor Agonist ◽

Rabbit Lung ◽

Hypotensive Action ◽

Duration Of Action ◽

Selective Agonist ◽

Comparable Magnitude

Abstract We recently identified a novel human B2 receptor (B2R) agonist [Hyp3,Thi5,NChg7,Thi8]-bradykinin (NG291) with greater in vitro and in vivo potency and duration of action than natural bradykinin (BK). Here, we further examined its stability and selectivity toward B2R. The hypotensive, antithrombotic, and profibrinolytic functions of NG291 relative to BK and its analogue ([Hyp3,Thi5,(4-Me)Tyr8(ΨCH2NH)Arg9]-BK) (RMP-7) were also tested. Contraction assays using isolated mouse stomachs (containing kinin B1R, B2R, and kininase I- and II-like activities) showed that NG291 is a more potent contractant than BK and is inhibited by HOE-140 (B2R antagonist) but unaffected by R954 (B1R antagonist), whereas both decreased the potency of BK. In stomach tissues from B2R knockout mice, BK maintained its activity via B1R, whereas NG291 had no contractile effect, indicating that it was selective for B2R. Unlike BK, NG291 was not degraded by rabbit lung ACE. Comparing intravenously administered BK and NG291 revealed that NG291 exhibited more potent and prolonged hypotensive action and greater antithrombotic and profibrinolytic activities. These effects were of comparable magnitude to RMP-7 and were absent in B2R knockout mice. We concluded that NG291 is a novel biostable B2R-selective agonist that may prove suitable for investigating the (pre)clinical cardioprotective efficacy of B2R activation.

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