Effects of Neuropeptides on Intestinal Ion Transport
Edwin E. Daniel in Neuropeptide Function in the Gastrointestinal Tract, 2019
However, if stimulation leads to release of both transmitters, potential for interactions occur. Campbell43 argues cogently that cotransmission involves the clear demonstration “that two or more coreleased transmitters act on the same target cell, so that the net result of transmission incorporates interactive effects of the transmitters”. His analysis thus holds both coexistence and corelease to be necessary but insufficient conditions for demonstrating cotransmission. Such interactions could be synergistic (additive) or antagonistic. Corelease may not necessarily imply release from the same site. In the feline jejunum, 5-HT and substance P were released into the lumen following vagal stimulation, but pharmacological antagonists were used to demonstrate that the release of the two transmitters was independent and from two different sources (the EC cell for 5-HT and peptidergic neurons for substance P).48
Biological Activities of Peptides in Brain Tissues
Gerard O’Cuinn in Metabolism of Brain Peptides, 2020
Neuropeptide Y (also known as neuropeptide tyrosine or NPY) was first identified by Tatemoto and Mutt8. This 36-amino-acid peptide is the most widely distributed of the neuropeptides discovered to date and has generated a huge number of scientific publications over the last decade. NPY fulfills the main neurotransmitter criteria: storage in synaptic granulae9, release triggered by electrical nerve stimulation10, action at specific receptors. Much of the research relating to NPY has concerned its coexistence with classic neurotransmitters (e.g., norepinephrine) and possible role in cotransmission, in line with the generally accepted view that neurons use multiple messenger molecules, at least one of which is usually a peptide. NPY has frequently been used to study cotransmission, particularly as a mediator of sympathetic neurotransmission in conjunction with the classic neurotransmitter norepinephrine.
Insulin and Brain Reward Systems
André Kleinridders in Physiological Consequences of Brain Insulin Action, 2023
It is perhaps too early to claim a sufficient understanding of the several roles of central insulin in physiology and disease. Nevertheless, in this chapter, we have attempted to focus on the central interactions of insulin and its receptors with dopaminergic neurotransmission and mesolimbic pathways, a system that is apparently coding for the reward value and reward prediction of stimuli like food and drugs of misuse. And the possible impact of such interactions on the phenotype of disorders with signature deficits of dopaminergic neurotransmission like addictive disorders, mood disorders, and Parkinson’s disease. The direct impact of insulin on major regulators of dopamine exocytosis, like the dopamine transporter, as well as the modulation of dopaminergic signaling by cellular and molecular mechanisms that reside with IRs in both neurons and astrocytes provide a good first insight into how central insulin functions and on possible new therapeutic approaches for these disorders that target central IRs.
GABA(A) receptor-targeted drug development -New perspectives in perioperative anesthesia
Published in Expert Opinion on Drug Discovery, 2019
Bernd Antkowiak, Gerhard Rammes
One promising candidate is the selective high affinity TSPO ligand XBD173 (AC-5216/emapunil) which exerts rapid anxiolytic effects in animal models and humans by elevating neurosteroids e.g. 3α,5α-THPROG [132]. XBD173 potentiated GABA-mediated synaptic transmission, which was prevented by finasteride [132]. These data provide further evidence that neurosteroidogenesis is involved in the differential effects of TSPO ligands on GABAergic neurotransmission. In contrast to the TSPO ligands RO5-4864 and PK95111, XBD173 has been clinically proven for efficacy, safety and tolerability also in humans. Thus, XBD173 might have a therapeutic potential for critical care medicine. The latter findings suggest that TSPO ligands have the potential to replace benzodiazepines in several clinical settings.
Towards a functional connectome in Drosophila
Published in Journal of Neurogenetics, 2020
In all animals, receptors situated at the postsynaptic density are not only modulated by pre-synaptically released neurotransmitters, but also by molecules and peptides released extrasynaptically or from other nearby presynaptic sites (Bentley et al., 2016; De-Miguel & Trueta, 2005; Lendvai & Vizi, 2008). Serotonergic neuromodulation occurs by both synaptic communication as well as volume release (Fuxe & Borroto-Escuela, 2016). In the adult fly, serotonin has been shown to nonsynaptically modulate optic lobe neurons (Gschweng et al., 2019). Serotonergic neurons in vertebrates and invertebrates have widespread impacts across different brain areas and modulate many different cells, sometimes in opposing manners. The mechanisms of volume-released neurotransmission can also involve glial cells that contribute by taking up neurotransmitters (Henn & Hamberger, 1971). Though non-synaptic neuromodulation cannot be predicted by the connectome, it can significantly influence neural processing and therefore the functional circuits that give rise to behavior (Bargmann, 2012; Bargmann & Marder, 2013; Marder, 2012).
New developments in pharmacotherapy for Friedreich ataxia
Published in Expert Opinion on Pharmacotherapy, 2019
Alexandra Clay, Patrick Hearle, Kim Schadt, David R. Lynch
Tak-831 inhibits D-amino acid oxidase, an enzyme which destroys D-amino acids such as D-serine in the brain [89]. D-serine functions as a coagonist at the NMDA receptor, a crucial CNS receptor for synaptic modification; increased D-serine levels are expected to enhance the function of the NMDA receptor and promote synaptic modification [89–91]. This distinguishes it from other symptomatic agents based on its ability to create long-term synaptic changes and to theoretically reinforce neurotransmission at favorable synapses. In addition to the co-agonist action with NMDA, D-serine also activates delta glutamate signaling, particularly in cerebellar neurons [89–91]. Thus, Tak-831 may ameliorate the cerebellar and neuronal deficits present in FRDA. In one FRDA mouse model Tak-831 partially reversed the loss of coordination, demonstrating proof of concept for a symptomatic trial of cerebellar dysfunction in humans [92]. A phase II clinical trial investigated the efficacy of high and low dose Tak-831 against placebo on upper limb function and manual dexterity using the 9-hole-peg test as well as other neurological performance assessments [62]. The study completed assessment in late 2018, but results from this trial are not yet available.
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