Resensitization

Theoretical models shed light on additional aspects of pulsatile cAMP signaling in Dictyostelium. First, like Ca + spikes, cAMP pulses are frequency encoded. Only pulses delivered at 5-min intervals are capable of accelerating slime mold development after starvation. Simulations indicate that frequency encoding is based on reversible receptor desensitization [76]. The kinetics of receptor resensitization dictates the interval between successive pulses required for a maximum relay response [78]. Second, cAMP oscillations in... 

In some cases, for example, in the case of the P -adrenergic receptor, internalization has been found to be a precursor to resensitization of the receptor (168,169). This phenomenon may be common to many GPCRs. Internalization may afford the opportunity of receptor dephosphorylation through the action of an endosomic acid phosphatase (170), resulting in resensitization of the receptor (171). 

Krueger, K. M., Daaka, Y., Pitcher, J. A., and Lefkowitz, R. J. (1997) The role of sequestration in G protein-coupled receptor resensitization. Regulation of beta2-adrenergic receptor dephosphorylation by vesicular acidification. J. Biol. Chem. 272, 5-8. 

Pippig, S., Andexinger, S., and Lohse, M. J. (1995) Sequestration and recycling of beta 2-adrenergic receptors permit receptor resensitization. Mol. Pharmacol. 47, 666-676. 

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. 

Normally, the acetylcholine concentration in the synaptic cleft is quickly lowered by the enzyme acetylcholinesterase, present in the cleft. When acetylcholine levels remain high for more than a few milliseconds, the receptor is desensitized (Fig. 12-lc). The receptor channel is converted to a third conformation (Fig. 12-4c) in which the channel is closed and the acetylcholine is very tightly bound. The slow release (in tens of milliseconds) of acetylcholine from its binding sites eventually allows the receptor to return to its resting state—closed and resensitized to acetylcholine levels. 

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... 

Backstrom JR, et al. Deletion of the serotonin 5-HT2C receptor PDZ recognition motif prevents receptor phosphorylation and delays resensitization of receptor responses. J Biol Chem 2000 275(31) 23,620-23,626. 

HT2C MUPP1 Facilitates receptor phosphorylation and resensitization Carboxyl terminus PDZ domain 238, 240, 241... 

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. 

However, it is clear that opioid receptor endocytosis is critical for the receptor to resensitize. Wolf et al. [170] reported the mutation of Thr394 of mu opioid receptor to Ala resulted in the rapid internalization and resensitization of receptor. Similar observations were reported with various spliced variants of mu opioid receptor, in which the rate of desensitization appears to correlate inversely with the resensitization properties of receptor [169]. Such observations and others have led to a hypothesis proposed by Whistler et al. [140] that the ability of various opioid agonists to produce tolerance is dependent on their RAVE values. In their hypothesis, agonist that induces rapid receptor internalization, e.g., etorphine, would develop less tolerance in animals than agonist such as morphine, which does not produce receptor... 

Resensitization Recovery of functional response after desensitization. 

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. 

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