China
Africa
Explore chapters and articles related to this topic
Role of central GABA in the regulation of blood pressure and the development of hypertension in the SHR
Published in H. Saito, Y. Yamori, M. Minami, S.H. Parvez, New Advances in SHR Research –, 2020
Maarten Van Den Buuse, Geoffrey A. Head
While most of the above mentioned studies on effects of muscimol in the ventrolateral medulla would suggest GAB A-A receptor-mediated phenomena, there is also some evidence for GABA-B receptor-mediated effects. Thus, micro-injection of baclofen into the rostral ventrolateral medulla caused a significant decrease in blood pressure and heart rate, whereas the GABA-B receptor antagonist 2-hydroxy-saclofen had the opposite effect (Avanzino et al., 1994), leading the authors to suggest a tonically active inhibitory mechanism in the ventrolateral medulla mediated by GABA-B receptors.
Neurotransmitters and pharmacology
Published in Mark J. Ashley, David A. Hovda, Traumatic Brain Injury, 2017
Ronald A. Browning, Richard W. Clough
There are several GABA antagonists available for experimental use. However, because all the GABAA antagonists are convulsants, they have no clinical use at the present time. The classical GABAA antagonist is bicuculline, but picrotoxin is also an antagonist. Saclofen and phaclofen are GABAB antagonists that are being used in experimental animals to help deduce the functional importance of the GABAB receptor. There are also a group of experimental compounds that bind to the benzodiazepine binding site on the chloride channel and cause a reduction in the effectiveness of GABA. The latter compounds, of which beta-carboline-3-carboxylic acid (and other beta carbolines) is an example, are called inverse agonists. Clearly, the GABA antagonists and the inverse benzodiazepine agonists are proconvulsant and have no clinical use in medicine. However, it is possible that such drugs may be developed for use in the TBI patient (see the following). Of clinical importance is flumazenil (Romazicon®), a specific antagonist at the benzodiazepine binding site on the GABA receptor that is used to reverse the effects of benzodiazepines in the treatment of toxicity from overdose.58
Serotonergic Mechanisms in Baroreceptor Afferent Processing and Cardiovascular Control By the NTS
Published in I. Robin A. Barraco, Nucleus of the Solitary Tract, 2019
Inhibition of the NTS second-order baroreceptor neurons, or of presynaptic intemeurons, by activation of 5-HT3 receptors might explain the baroreceptor blocking action of 5-HT (nmol) or 5-HT3 agonists. However, 5-HT3 receptors are known to mediate excitatory actions of 5-HT on target cells.62-64 Accordingly, a probable explanation for the inhibition of the baroreceptor reflex by the activation of 5-HT3 receptors located on vagal afferents, is that this activation produces a local depolarization and consequently decreases neuronal transmission through a presynaptic inhibitory mechanism. This could explain the discrepancy between results showing that the stimulation of 5-HT3 receptors located on vagal afferent fibers elicited baroreceptor-like responses65 and our results described above showing that the stimulation of 5-HT3 receptors located on the central terminals of these fibers produced opposite effects. However, another possible explanation is that different vagal fibers are involved in the CV effects induced by the stimulation of peripheral vs. central (NTS) 5-HT3 receptors. Thus, release of the neurotransmitter from certain vagal afferents by activation of 5-HT3 receptors located on the terminals of these afferents in the NTS could inhibit barosensitive neurons, directly or indirectly, by the activation of a local inhibitory system. There is some evidence to support this hypothesis. Inhibitory GABAergic neurons have been found in the NTS66,67 and it has also been shown that pharmacological stimulation of GABAA or GABAB receptors in the NTS produced the same CV effects as the stimulation of 5-HT3 receptors: an increase in BP and a baroreceptor reflex inhibition.68-71 Nodose ganglionectomy decreased the level of GABA in the NTS, but a peripheral origin of the NTS GABAergic innervation seems unlikely since very low levels of GABA have been observed in the NG.72 Thus, the decrease in GABA levels in the NTS after ganglionectomy can be interpreted as a consequence of a transsynaptic degeneration. Consequently, a direct connection between peripheral afferents and GABAergic neuronal elements in the NTS can be postulated. In addition, we have shown that the bilateral microinjection of a GABAA receptor antagonist, bicuculline into the NTS prevented all the CV effects of the subsequent local administration of nanomolar doses of 5-HT.50 This inhibition of the CV effects of 5-HT was not observed after the prior microinjection of a postsynaptic GABAB receptor antagonist, 8-OH-saclofen.77
Updated review on the link between cortical spreading depression and headache disorders
Published in Expert Review of Neurotherapeutics, 2021
Doga Vuralli, Hulya Karatas, Muge Yemisci, Hayrunnisa Bolay
Single pulse transcranial magnetic stimulation (sTMS) was shown to be effective for the acute attack treatment in migraine [177]. Potential mechanisms of action of TMS were investigated in animal models of migraine. Lloyd et al. assessed the cortical actions of sTMS treatment [178]. sTMS neither excited cortical neurons nor changed cortical blood vessel diameter. However, sTMS effected the CSD characteristics. The potential actions of sTMS on CSD with GCaMP fluorescence recordings in Snap25-2A-GCaMP6s-D mice were evaluated when CSD was initiated after sTMS stimulation. The peak fluorescence, the area under the curve of the CSD, and the resolution from peak to baseline were significantly reduced in the active sTMS group compared to sham group. Moreover, in the same study, two consecutive sTMS pulses applied at ~ 0.92 T and ~ 1.1 significantly decreased spontaneous neuronal firing with a maximum reduction at ~1.1 T at 75 min post-TMS. Two consecutive sTMS pulses at ~ 1.1 T significantly decreased L-glutamate-evoked firing, but, not in the presence of the GABA antagonists bicuculline or saclofen. Two consecutive sTMS pulses at ~1.1 T resulted in a two-fold increase in electrical stimulation thresholds for CSD in rats compared to baseline. In a different experimental group, the electrical threshold was found to be higher in active sTMS treatment group compared to sham-treated group but not in the presence of GABA antagonists bicuculline or saclofen [178]. sTMS at similar intensities used in the treatment of migraine reduced the spontaneous cortical neuronal activity and supressed CSD with a possible interaction with GABAergic circuits rather than directly supressing glutamatergic activity.