Identification Of Receptors In Vitro
William C. Eckelman, Lelio G. Colombetti in Receptor-Binding Radiotracers, 2019
This criterion for the identification of a binding site as a receptor is discussed in the chapter by Kuhar. Briefly, binding activity must be located in the places where the physiological response is found, and nowhere else. This criterion can be used at different levels. An extremely crude application is that a neurotransmitter receptor should be located in the nervous system (or some target organ). If the receptor is known to be present in certain areas of the nervous system (e.g., in certain brain nuclei), it should be present in higher levels there than in the rest of the nervous system. More sophisticated localization of binding, particularly demonstration that the binding activity is located at the synapse, where neurotransmitter receptors should be concentrated, requires histochemical or autoradiographic techniques, rather than the biochemical binding methods that are the focus of this chapter.
The Central Nervous System Organization of Behavior
Rolland S. Parker in Concussive Brain Trauma, 2016
Cells communicate with each other to coordinate their functions. The neuron-receiving neurotransmitters are not passive recipients of this information. The message is determined by both the neurotransmitter receptors and the neurotransmitters themselves. In fact, there are more types of neurotransmitter receptors than neurotransmitters (Knapp et al., 2003). Receptors are proteins within the cell membrane to which substances bind; these are known generically as ligands. If neurotransmitters, hormones, and paracrine signals are considered the first messengers binding to a receptor, intracellular changes create second messengers that diffuse through the cell and change the activity of the intracellular effector system (Barabam, 2005; Changeux, 1993; Junqueira & Carneiro, 2005; Marks et al., 1996, pp. 679–685). Target cells are those that have specific receptors for a signal (e.g., neurotransmitter or hormone) and do not bind to other hormones. Different types of target cells contain different numbers of receptors for a particular hormone, varying from less than 100 to more than a million/cell. Receptor subtypes meditate different behaviors and response to particular medications (e.g., anticonvulsants and anxiolytics) (Zorumski et al., 2005). The receptor density determines the physiological response. Receptor characteristics influence physiological regulation and drug actions (intended and side effects).
Studies on the Neurobiology of Depression
Siegfried Kasper, Johan A. den Boer, J. M. Ad Sitsen in Handbook of Depression and Anxiety, 2003
Neurotransmission in the noradrenergic system is mediated by a number of different neurotransmitter receptors whose function has been implicated in either the pathophysiology of depression or in the mechanism of action of antidepressants. The α2-adrenergic receptors and β-adrenergic receptors have been the focus of considerable research on their role in the pathophysiology of depression. Increased α2-receptor density is seen in the brains of suicide victims [218]. Treatment with antidepressants has been associated with decreases in the density and sensitivity of these receptors on platelets. Several methods have been used to investigate the role of the α2-receptor in depression. An indirect method for studying α2-receptors is to challenge subjects with the α2-receptor agonist clonidine. Administration of clonidine induces growth hormone secretion, primarily through post- synaptic α2-receptors. Several abnormalities in growth hormone release in patients with major depression have been reported. Growth hormone response to clonidine is blunted in unipolar depressed patients [202,321,322], supporting the concept of decreased responsiveness of postsynaptic α2-adrenergic receptors in depressed patients.
CBF regulation in hypertension and Alzheimer’s disease
Published in Clinical and Experimental Hypertension, 2020
Noushin Yazdani, Mark S. Kindy, Saeid Taheri
NE preferentially binds α1-adrenoreceptors to cause VSMCs contraction which increases vessel tone and resistance (80). In normotensive human α1-adrenoreceptor blocker does not influence CBF (81). Even in mild hypertensive humans, vascular α-receptor sensitivity to NE remains unchanged (82). However, in both patients with primary hypertension (83) as well as in AD patients (84) autoantibody of α1-adrenoreceptor was found. Of note is that there is heterogeneity in the expression of neurotransmitter receptors across the cerebrovascular tree that causes different actions with the same neurotransmitter. For example, there is a shift in receptor population from α- to β-adrenoreceptors in penetrating arterioles. NE activation of α1-adrenoreceptors causes major cranial arteries such as middle cerebral artery contraction (85), but NE activation of β-adrenoreceptors causes penetrating arterioles dilation (86). Moreover, Aβ accumulation has been shown in animal models that activate α1-adrenoreceptors (87). Therefore, we cannot assume that parenchymal and pial arteries will behave similarly when challenged with an increase in blood pressures and Aβ accumulation. It has become evident that the depletion of central and peripheral catecholamine stores could prevent or attenuate the development of hypertension (88).
Association between ABCB1 polymorphisms and response to first-generation antiepileptic drugs in a Tunisian epileptic population
Published in International Journal of Neuroscience, 2018
Marwa Ajmi, Sana Boujaafar, Nadia Zouari, Dorra Amor, Asma Nasr, Nabila Ben Rejeb, Sana Ben Amor, Asma Omezzine, Sofien Benammou, Ali Bouslama
Our results showed that focal and focal to bilateral tonic-clonic seizures appeared to be more resistant than generalized seizures (54.4% vs 45.6%, p = 0.144). Some studies reported same results [38,40,42]. Drug-resistant epilepsies include about 60% of focal epilepsies [34,35,43,44]. However, most descriptive studies classified patients according to the previous classification and mentioned a clear predominance of generalized seizures [39,45,46]. Indeed, a careful interrogation and an oriented clinical investigation can identify a focal beginning. In our population, an etiology was found in 71% of cases, we observed that the structural etiology (47.8%) seemed to be more frequent followed by genetic (13.2%) and infectious (10.8%) etiologies. Mechanisms explaining this pharmaco-resistance referred to reduced target sensitivity that may occur through the alterations of the composition and functionality of voltage-gated ion channels or neurotransmitter receptors in epileptogenic brain tissue [10,47–50]. Epileptic syndromes represented 33.5% (p = 0.358), this restrain number could be due to the difficulty of accessing to the EEG.
5-HT1A receptor ligands and their therapeutic applications: review of new patents
Published in Expert Opinion on Therapeutic Patents, 2018
Jakub Staroń, Ryszard Bugno, Adam S. Hogendorf, Andrzej J. Bojarski
Flibanserin (Addyi) was originally developed by Boehringer Ingelheim and Sprout Pharmaceuticals to treat depression, but the indication has finally been changed to a first-in-class nonhormonal medicine used to treat hypoactive sexual desire disorder in women (HSDD) [32,33]. After a long and controversial process, the so-called “Female Viagra” was approved by the FDA in 2015 [34,35]. Flibanserin shows a high affinity for serotonin receptors in the brain: it acts as an agonist on 5-HT1AR and an antagonist on 5-HT2AR. It also moderately antagonizes dopamine D4R and serotonin 5-HT2BR and 5-HT2CR. Its action on neurotransmitter receptors may contribute to a reduction in serotonin levels and an increase in dopamine and norepinephrine levels, all of which may play a part in reward processing [36].
Related Knowledge Centers
- Action Potential
- Autoreceptor
- Axon
- Cell Signaling
- Chemical Synapse
- Synapse
- Neurotransmitter
- Ion Channel
- Receptor
- Neural Circuit