Chemokine Receptor Expression and Regulatory Mechanisms
Thomas R. O’Brien in Chemokine Receptors and AIDS, 2019
Desensitization is defined as diminished responsiveness of a signaling system to subsequent stimuli following initial stimulation (48). The mechanism of G-protein-coupled receptor desensitization has been studied in great detail for the visual and adrenergic systems (48, 49). From these studies, two types of desensitization, termed “homologous” and “heterologous,” have been described. Homologous desensitization occurs in receptors in the agonist-occupied state and involves phosphorylation by G-protein-coupled receptor kinases. Several of the G-protein-coupled receptor kinases were identified in leukocytes (50). Homologously phosphorylated receptors associate with members of the arrestin family of proteins which results in a decreased affinity of the receptor for G-proteins and in receptor internalization.
An Investigation in Vitro of the Properties of the Individual Muscle Layers of the Rabbit Colon in an Induced Colitis.
William J. Snape, Stephen M. Collins in Effects of Immune Cells and Inflammation on Smooth Muscle and Enteric Nerves, 2020
The intracellular basis of the phenomenon of desensitization has been studied in a number of physiological systems including vascular smooth muscle23–26, cardiac muscle27,28, skeletal muscle29–31, tracheal smooth muscle32 and neuronal tissue33. From these various studies it is clear that the mechanisms underlying desensitization are extremely diverse and vary from one receptor type to another, even within the same tissue. Thus, for example, the rapid desensitization of nicotinic cholinergic receptors in skeletal muscle occurs as a result of phosphorylation of the receptor via cAMP-dependent protein kinase (kinase A)29. In contrast, desensitization of skeletal muscle β – adrenoreceptors is reported to result from 70–80% of the receptors being internalized (sequestered) by the cell34.
Supersensitivity and Desensitization
Kenneth J. Broadley in Autonomic Pharmacology, 2017
Acute tachyphylaxis or desensitization. The progressive loss of sensitivity to an agonist either with repeated exposure or in its continuous presence is desensitization or tachyphylaxis. The progressive reduction of tissue sensitivity to an indirectly acting sympathomimetic amine with repeated exposure is a special case of tachyphylaxis attributable to the loss of available stores of noradrenaline in superficial storage vesicles (Figure 4.1, Chapter 4). The term desensitization is usually applied to the phenomenon of a diminished functional responsiveness of the tissue to an agonist, despite the continued presence of that agonist (Figure 14.1). This process can occur rapidly within minutes or more slowly over a matter of hours or days. There has been considerable work on the process of desensitization of G protein-coupled receptors, much of which has centred on the β-adrenoceptor. The next sections of this chapter will therefore concentrate on the mechanisms of desensitization, dealing with both the acute and chronic phases of the process.
Predicting future performance in medical students. A longitudinal study examining the effects of resilience on low and higher performing students
Published in Medical Teacher, 2019
Sarath Burgis-Kasthala, Nicholas Elmitt, Lillian Smyth, Malcolm Moore
Carver describes different types of potential response. Firstly, desensitization describes subsequent exposures to similar adversity resulting in a lower initial impairment; this is linked to confidence and the individual sense of mastery of a situation (or self-efficacy). Individuals with higher confidence are more likely to seek instrumental forms of coping with the stress whereas those with lower confidence are more likely to exhibit avoidance behaviors. These individuals are more likely to be sensitized by further adversities resulting in greater initial impairment. Secondly, individuals may have an equal initial impairment but may respond (bounce back) more quickly. Subsequent exposures may improve the speed of recovery for example by developing pathways to knowledge, skills, knowledge, and knowledge of resources. Finally, he describes four potential end-points: burnout—an almost complete loss of functional ability, surviving with impairment (impaired functional ability) resilience (returning to previous function), and thriving (improved functional ability).
A general strategy for de novo immunotherapy design: the active treatment of food allergy
Published in Expert Review of Clinical Immunology, 2018
Stefania Arasi, Lucia Caminiti, Giuseppe Crisafulli, Giovanni Battista Pajno
OIT involves ingesting gradually increasing doses of allergenic food and represents the most effective route of administration to induce desensitization to foods, including milk, egg, and peanut. Whether OIT can induce post-desensitization effectiveness is still controversial [16]. Currently, oral desensitization represents the first step toward a permanent tolerance or post-desensitization effectiveness. As with other kinds of immunotherapy (i.e. for environmental allergenes), the duration of desensitization could be pivotal for achieving post-desensitization effectiveness. It is reasonable to think that in developed countries, the almost continuous or frequent ingestion of foods – such as CM or HE – usually present in the diet, after the achievement of desensitization is per se easy to do by patients; therefore, active specific immunotherapy might be permanently successful for some food allergens, even without long periods of withdrawal. In other words, in good clinical practice for foods such as milk and egg, after the achievement of desensitization, the chance of friendly accompanying patient to post-desensitization effectiveness (tolerance) represents a possible therapeutical option. Of note, long enough trials with appropriate controls on post-desensitization effectiveness are awaited.
Examining the Relation between Self-reported ASD Symptoms and Sensory Sensitivities from a Community-based Sample of Adults
Published in Developmental Neurorehabilitation, 2021
Lucy Barnard-Brak, Laci Watkins, David M. Richman
The first hypothesis is that habituation explains sensory sensitivities. Habituation is the process that results in reduced responding (desensitization) to a stimulus presented in the same manner repeatedly.8 For instance, a child who repetitively strokes an object may develop a hypo- or under-responsivity to that sensory stimulus and other similar stimuli through the natural process of habituation to environmental stimuli,8published a pioneering article conceptualizing the dual-process theory of habituation: decremental (habituation) and incremental (sensitization). We refer interested readers to,9for a more contemporary review of habituation and sensitization. Relative to atypical behavior in response to sensory stimulation for individuals with ASD, one plausible hypothesis is that the repetitive behavior causes repeated sensory stimulation directly produced by engaging in the behavior and the organism’s tactile responses may decrease to the same level of sensory stimulation produced by the repetitive behavior. Self-injurious behaviors (i.e., behaviors that produce self-inflicted tissue damage) are not a feature of ASD per DSM-5 diagnostic criteria, but, due to the oftentimes restricted and repetitive nature of some forms of these behaviors, they are often considered to be a related feature of the disorder. It is estimated that 30% of individuals with ASD engage in self-injurious behaviors and a sub-portion of these cases are maintained by automatic positive or automatic negative reinforcement.10–17
Related Knowledge Centers
- Diabetes
- Drug Tolerance
- Allergy
- Phosphorylation
- Receptor
- Adrenergic Receptor
- Agonist
- Pharmacology
- G Protein-Coupled Receptor Kinase 2
- Dose