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Neural Regulation of Coronary Blood Flow*
Published in Irving H. Zucker, Joseph P. Gilmore, Reflex Control of the Circulation, 2020
David D. Gutterman, Michael J. Brody, Melvin L. Marcus
Segal et al. (1981) described an increase in heart rate, arterial pressure, and coronary vascular resistance to intracerebroventricular injections of bicuculline in anesthetized cats. Following cardiac sympathetic denervation, bicuculline produced no increase in coronary vascular resistance, indicating a neural mechanism. Similarly, intracerebroventricular injections of digoxin produces a sustained coronary vasoconstriction of neural etiology (Garan et al., 1974). The central site activated by digitalis to produce coronary vasoconstriction has been localized to the caudal medulla near the obex. Specifically, it appears that digitalis administered peripherally or into the cerebral ventricles crosses the blood barrier near the obex to activate cell bodies within the area postrema (Somberg et al. 1981; Hamlin et al. 1974; Somberg, 1984, 1985). Activation of neurons in this region produces a neurally mediated coronary vasoconstriction (Gatti et al., 1988). It has been hypothesized that the coronary vasoconstrictor effect of digitalis may contribute to its arrhythmogenic properties, and adverse effects in patients with myocardial infarction and ischemia.
Neurotransmitters and Receptors in the Basal Ganglia
Published in W. R. Wayne Martin, Functional Imaging in Movement Disorders, 2019
GABA is the neurotransmitter used by the majority of neurons in the striatum, lateral and medial pallidum, and the substantia nigra pars reticulata.23,24 Two classes of GABA receptors have been defined, GABAA and GABAB receptors. The GABAA receptors are postsynaptic receptors mediating chloride flux. These receptors are bicuculline-sensitive and are the classic GABA receptors mediating GABAergic inhibition. GABAB receptors also appear to mediate inhibition but through bicuculline-insensitive receptors. The GABAB receptor is located both presynaptically on the terminals of neurons which use transmitters other than GABA and postsynaptically. There are no selective antagonists at the GABAB receptor and the only selective agonist is baclofen.
The Epileptic Baboon, Hypothetical Neuronal Network and Action of Anticonvulsant Drugs
Published in Carl L. Faingold, Gerhard H. Fromm, Drugs for Control of Epilepsy:, 2019
Christian Menini, Carmen Silva-Barrat, Robert Naquet
Compounds that act at the GABA recognition site in the receptor complex reproduce the effects of GABA. GABAA agonists are compounds that selectively bind to the postsynaptic receptor to open chloride channel and whose effects are antagonized by bicuculline. Surprisingly, these drugs (muscimol, THIP) do not suppress ILS-induced PD in baboons97,98 and favor the occurrence of spontaneous PD.99,100 GABAB agonists are compounds that selectively bind to the presynaptic receptor, decrease calcium entry and neurotransmitter release, and whose effects are insensitive to bicuculline. These drugs (baclofen) diminish or suppress ILS-induced epileptic manifestations in baboons.100,101 Progabide, which acts on both types of GABA receptors, also decreases photosensitivity of baboons.102,103
3D bioprinting for organ and organoid models and disease modeling
Published in Expert Opinion on Drug Discovery, 2023
Amanda C. Juraski, Sonali Sharma, Sydney Sparanese, Victor A. da Silva, Julie Wong, Zachary Laksman, Ryan Flannigan, Leili Rohani, Stephanie M. Willerth
The intrinsic complexity of the central nervous system (CNS) limits its ability to be replicated using current in vitro 2D models. Accordingly, 3D bioprinting tissue models play an important role in the process of modeling CNS diseases with applications in drug screening. Pharmaceutical research for complex brain diseases, such as Alzheimer’s Disease and Parkinson’s Disease, is often limited by expenses, time, and inadequate pre-clinical models. 3D bioprinting techniques allow for cell-cell interactions that more accurately replicate in vivo tissues, thus offering an improved approach for brain disease modeling and drug screening platform. A study by Gu et al (2018) [13] bioprinted brain organoids with differentiated neurons derived from human neural stem cells (hNSC). The hNSC were well distributed along the organoid and displayed markers for both neuronal and neuroglial markers. They also observed upregulated GABAergic and serotonin neuronal markers, as well as vesicular glutamate and serotonin transporters. Neuronal maturation was observed by both spontaneous and bicuculline (a GABA(A) receptor antagonist) induced calcium response. Mature neurons displayed spontaneous activity, synaptic contacts and established networks. While GABAergic differentiation was predominant, the presence of both glutamatergic and serotonergic activity indicates that the model could be used as a more extensive physiological model that could be used for CNS-oriented drug screening.
Taurine and GABA neurotransmitter receptors, a relationship with therapeutic potential?
Published in Expert Review of Neurotherapeutics, 2019
Lenin Ochoa-de la Paz, Edgar Zenteno, Rosario Gulias-Cañizo, Hugo Quiroz-Mercado
γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter of the mammalian CNS. GABA exerts its inhibitory effect through two types of specific receptors called GABAA (ionotropic) and GABAB (metabotropic). The complexity of GABAA receptors lies in the number of subunits they have and in the different combinations in which they assemble, as well as in the variants generated by RNA splicing or editing [3]. To date, six α, three β, three γ, three ρ, and one δ, ε, π, and θ subunits have been characterized, which gives this receptor a high degree of heterogeneity. In general, GABAAR are selectively blocked by bicuculline and picrotoxin, and they are allosterically modulated by neurosteroids, barbiturates, and benzodiazepines. The metabotropic GABA receptors (GABABR) are heterodimers composed of two subunits, GABABR1 and GABABR2. These receptors are mainly coupled to type Giα and Goα proteins, and they are insensitive to bicuculline but are inhibited by phaclofen. Despite their poor structural diversity, GABABR present a very varied kinetic and pharmacological response.
Effects of long-term exercise and low-level inhibition of GABAergic synapses on motor control and the expression of BDNF in the motor related cortex
Published in Neurological Research, 2018
Takahiro Inoue, Shuta Ninuma, Masataka Hayashi, Akane Okuda, Tadayoshi Asaka, Hiroshi Maejima
The latency to fall in the rotarod test is shown in Figure 2(A). Two-way ANOVA showed a significant factorial effect of exercise and no significant two-factor interaction, demonstrating that exercise improved the balance coordination either in the presence or in the absence of GABAA receptor inhibition. The latency to fall in the wire hang test is shown in Figure 2(B). Two-way ANOVA showed a significant factorial effect of bicuculline administration and no significant two-factor interaction, demonstrating that the inhibition of GABAA receptor weakened muscular function either in the presence or in the absence of exercise.