Pineda J, Ruiz-Ortega JA, Martin-Ruiz R, Ugedo L. Agmatine does not have activity at alpha 2-adrenoceptors which modulate the firing rate of locus coeruleus neurons: an electrophysiological study in rat. Neurosci Lett 219: 103-106
Agmatine (decarboxylated arginine) has been proposed as an endogenous ligand for non-adrenoceptor, imidazoline binding sites, but also binds to α2-adrenoceptors. The interaction of agmatine with α2-adrenoceptors was evaluated by studying the effect of agmatine on the firing rate of locus coeruleus (LC) neurones using extracellular recordings in anesthetized rats and rat brain slices. In vivo, local application of agmatine into the LC caused a slight and short-lasting increase in cell firing rate (P < 0.005). In vitro, agmatine failed to change the firing rate of LC neurones nor did it antagonize the inhibitory effect of noradrenaline on these cells. Since α2-adrenoceptors are known to inhibit the firing of LC cells, we conclude that agmatine does not have agonist or antagonist properties at α2-adrenoceptors of these neurones.
"Single-unit extracellular recordings of LC neurons were performed in slices from saline treated (WT n = 16 and TgNTRK3 n = 12) and morphine-treated (WT n = 16; TgNTRK3 n = 16) mice, as previously described (Pineda et al., 1996) and following the increasing dose morphine injection schedule of Section " Naloxone-precipitated morphine withdrawal after increasing doses of morphine " . Briefl y, mice were anesthetized with chloral hydrate (400 mg/kg, i.p.) and decapitated 1–4 h after the last injection of morphine. "
[Show abstract][Hide abstract] ABSTRACT: Panic disorder is a highly prevalent neuropsychiatric disorder that shows co-occurrence with substance abuse. Here, we demonstrate that TrkC, the high-affinity receptor for neurotrophin-3, is a key molecule involved in panic disorder and opiate dependence, using a transgenic mouse model (TgNTRK3). Constitutive TrkC overexpression in TgNTRK3 mice dramatically alters spontaneous firing rates of locus coeruleus (LC) neurons and the response of the noradrenergic system to chronic opiate exposure, possibly related to the altered regulation of neurotrophic peptides observed. Notably, TgNTRK3 LC neurons showed an increased firing rate in saline-treated conditions and profound abnormalities in their response to met(5)-enkephalin. Behaviorally, chronic morphine administration induced a significantly increased withdrawal syndrome in TgNTRK3 mice. In conclusion, we show here that the NT-3/TrkC system is an important regulator of neuronal firing in LC and could contribute to the adaptations of the noradrenergic system in response to chronic opiate exposure. Moreover, our results indicate that TrkC is involved in the molecular and cellular changes in noradrenergic neurons underlying both panic attacks and opiate dependence and support a functional endogenous opioid deficit in panic disorder patients.
"Extracellular recordings. Single-unit extracellular recordings of LC cells were made as previously described (Pineda et al., 1996). The recording electrode, which consisted of an Omegadot glass micropipette, was pulled and filled with NaCl (0.05 mol·L -1 ). "
[Show abstract][Hide abstract] ABSTRACT: Locus coeruleus (LC) neurons respond to sensory stimuli with a glutamate-triggered burst of spikes followed by an inhibition. The aim of our work was to characterize the inhibitory effect of glutamate in the LC.
Single-unit extracellular and patch-clamp recordings were performed to examine glutamate responses in rat brain slices containing the LC.
Glutamate caused an initial activation followed by a late post-activation inhibition (PAI). Both effects were blocked by an AMPA/kainate receptor antagonist but not by NMDA or metabotropic glutamate receptor antagonists. All glutamate receptor agonists were able to activate neurons, but only AMPA and quisqualate caused inhibition. In neurons clamped at -60 mV, glutamate and AMPA induced inward, followed by outward, currents, with the latter reversing polarity at -110 mV. Glutamate-induced PAI was not modified by alpha(2)-adrenoceptor, micro opioid, A(1) adenosine and GABA(A/B) receptor antagonists or Ca(2+)-dependent release blockade, but it was reduced by raising the extracellular K(+) concentration. Glutamate-induced PAI was not affected by several potassium channel, Na(+)/K(+) pump, PKC and neuronal NO synthase inhibitors or lowering the extracellular Ca(2+) concentration. The Na(+)-activated K channel opener bithionol concentration-dependently potentiated glutamate-induced PAI, whereas partial (80%) Na(+) replacement reduced glutamate- and AMPA-induced PAI. Finally, reverse transcription polymerase chain reaction assays showed the presence of mRNA for the Ca(2+)-impermeable GluR2 subunit in the LC.
Glutamate induces a late PAI in the LC, which may be mediated by a novel postsynaptic Na(+)-dependent K(+) current triggered by AMPA/kainate receptors.
British Journal of Pharmacology 03/2009; 156(4):649-61. DOI:10.1111/j.1476-5381.2008.00004.x · 4.84 Impact Factor
"Despite some affinity for imidazoline receptors and a -adrenoceptors, clear actions of agmatine at 2 Ž these receptors have not been described Pinthong et al., . 1995; Pineda et al., 1996 . Furthermore, agmatine has a range of other actions, from inhibition of NMDA channels to inhibition of nitric oxide synthase, that might be of Ž physiological importance Auguet et al., 1995, Reis and . "
[Show abstract][Hide abstract] ABSTRACT: In this article we outline the highlights of this special issue of the journal containing a series of articles covering many aspects of current interest in the field of imidazoline receptor research. This volume is the result of an international symposium held in September 1997 in Melbourne as an official satellite of the inaugural meeting of the International Society of Autonomic Neurosciences held in Cairns, Australia. A wide range of topics relating to imidazoline receptors were canvassed, including endogenous and synthetic ligands, identification and localisation of binding sites, putative transduction mechanisms and experimental and clinical functional studies.
Journal of the Autonomic Nervous System 11/1998; 72(2-3):74-9. DOI:10.1016/S0165-1838(98)00090-3
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