Desensitization and Resensitization

It would be interesting to know whether the acquired general desensitization is lasting. In any case, we can say that, in comparison to the control group, the desensitized guinea pigs are relatively less sensitive. This difference is macroscopically, as well as histologically verifiable. 

Lowney (1964) confirmed that hyposensitization in guinea pigs lasts at least from 5 weeks to 2 months. 

It is also interesting to establish whether desensitized guinea pigs can be resensitized with the same eczema-producing substance. 

guinea pigs sensitized to DNCB and then desensitized to DNCB, 

In each of the 3 groups we performed a sensitization treatment by our usual method  

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Beyer, A., Koch, T., Schroder, H., Schulz, S and HoUt, V. (2004) Effect of the Al 18G polymorphism on binding affinity, potency and agonist-mediated endocytosis, desensitization, and resensitization of the human mu-opioid receptor. J. Neurochem. 89, 553-560. 

Growth cones are subject to both chemoattractant and chemorepellent effects of guidance molecules and also to attraction or repulsion resulting from cell cell-contacts. To complicate the picture further, the netrins and also the brain-derived neurotrophic factor BDNF (see Fig. 30-6D) may first attract, and then after a period of adaptation or desensitization, repel a growth cone.4 13 4 4 446 443 Consecutive phases of desensitization and resensitization may result in a zig zag path of... 

Trincavelli ML, Tuscano D, Cecchetti P, Falleni A, Benzi L, Klotz K-N, Gremigni V, Cattabeni F, Lucacchini A, Martini C (2000) Agonist-induced internalization and recycling of the human A3 adenosine receptors role in receptor desensitization and resensitization. J Neurochem 75(4) 1493—1501... 

Gray JA, Sheffler DJ, Bhatnagar A, et al. Cell-type specific effects of endocytosis inhibitors on 5-hydroxytryptamine(2A) receptor desensitization and resensitization reveal an arrestin-, GRK2-, and GRK5-independent mode of regulation in human embryonic kidney 293 cells. Mol Pharmacol 2001 60 1020-1030. 

Here we provide the basic methods we use to study chemokine-receptor trafficking. These methods have been used in conjunction with chemokines and chemokine antagonists, and with other agents (e.g., phorbol esters) that can induce receptor endocytosis. In the following protocols, we refer only to the use of chemokines. We use the operational terms endocytosis and recycling to avoid alternative expressions such as down-modulation or down-regulation, desensitization, and resensitization, which may be used to reflect the functional state of the receptor or cell. 

Lin F, Wang H, Malbon CC. Gravin-mediated formation of signaling complexes in pradrenergic receptor desensitization and resensitization. J Biol Chem 2000 275 19,025-19,034. 

Equations (8.2) admit a unique steady state, which is always stable. In the simple, general case where the binding and dissociation of the ligand are much faster than the processes of desensitization and resensitization of the receptor, eqns (8.2) and (8.3) reduce to a single differential equation governing the time evolution of the system. The integration of that equation yields an analytical expression for the four receptor forms in the course of time (Segel et ai, 1986). 

Fig. 8.14. Dependence of the optimal pattern of pulsatile stimulation on the kinetics of receptor desensitization and resensitization. Shown are the variation of the optimal dmation Tj and optimal interval Tq as a function of the desensitization rate constant Atj (b) and resensitization rate constant k (a) (Li Goldbeter, 1989b).

The values of tq and Tj that define the optimal pattern are markedly influenced by the parameters that govern receptor desensitization and resensitization. In the model, these processes depend primarily on the rate constants Ic and k., respectively. Table 8.1 indicates how a change in either one or both of these constants affects the values of Tq and Ti. A comparison of rows and columns in table 8.1 shows that a five-fold increase (decrease) in kj leads to a decrease (increase) in t, by a roughly similar factor, while a similar result holds for Tq as a function of k i-... 

Table 8.1. Dependence of the optimum pattern of stimulation (tj, t2 ) (in min) on the rate constants of receptor desensitization and resensitization (k i)...

On the other hand, histological examination reveals a definite difference between the first group, which was desensitized and resensitized, and the other 2 groups. 

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