Desensitization phenomenon

In the x-ray structure of rhodopsin, an amphipathic helix runs parallel to the membrane from the intracellular end of TM-VII beneath the seven-helical bundle to the other side of TM-I and TM-II. At this point, one or more Cys residues are often found and are known to be subject to a dynamic posttranslational modification with palmitic acid residues. Like the phosphorylation event, the palmitoylation process appears to be dynamically regulated by receptor occupancy and is also involved in the desensitization phenomenon. The two posttranslational modifications can influence each other. For example, the conformational constraint induced by palmitoylation may alter the accessibility of certain phosphorylation sites. Like the phosphorylation process, the functional consequences of palmitoylation also appear to vary from receptor to receptor. 

Bk has been shown to stimulate histamine release from isolated peritoneal rat mast cells [30, 87] and this secretory response, like that elicited by other peptides, requires a source of metabolic energy and is prevented by depletion of cellular Ca [30, 87]. The subsequent treatment of such cellular Ca-depleted mast cells with Bk produces an inactivation or desensitization phenomenon to the subsequent addition of extracellular Ca (secretion declines as the time... 

The opposite phenomenon, a decrease of sensitivity, is known as desensitization. The main reasons for densensitization ate the results of relative electron level positions as weU as the secondary processes of the photoelectrons, for example (97),... 

Tachyphylaxis is a loss of drug efficiency which develops in minutes or hours. Transmitter depletion and receptor desensitization are the basic mechanisms of this phenomenon. 

While reproducible for many receptors, this phenomenon is not universal for GPCRs. For example, in the case of the M2 muscarinic receptor, while two-thirds of intracellular loop clusters of Ser/Thr residues ( Ser- "Ser and " Thr- "Ser) mediate internalization, only the carboxyl terminal ( Thr- "Ser) cluster mediates desensitization (136). In conclusion, internalization may follow desensitization, or it may occur independently (160) with or without the influence of other regulatory processes (161). 

J. Eadie reported in Ref 71 that the shock sensitivity of HMX/wax compacts is found to decrease as the amount of the HMX surface coated with wax increased. This thus indicates that the shock sensitivity depends on the surface area of the reactive expl exposed to reaction products. Similar results were observed 20 years earlier and reported in Ref 26. The following is a quote from this Ref, It was noted in the course of this work that the quantity of inert material per se was not the important factor in the phenomenon of desensitization. As a matter of fact, it was the thoroughness with which the explosive crystals (PETN) were coated that appeared to be an important factor in desensitization. Table 6 contains the results of the impact sensitivity tests conducted on PETN-wax mixts where both the quantity of wax in the mix and the degree of coating on the expl crystal are taken into account... 

Desensitization of receptors Prolonged exposure to the catecholamines reduces the responsivity of these receptors, a phenomenon known as desensitization. Three mechanisms have been suggested to explain this phenomenon (1) sequestration of the receptors so that they are unavailable for interaction with the ligand (2) down-regulation, that is, a disappearance of the receptor either by destruction or decreased synthesis and (3) inability to couple to G-protein because the receptor has been phosphory-lated on the cytoplasmic side by either protein kinase A or p adrenergic receptor kinase (PARK). 

An aspect of NAR function that is very important in its pharmacological manipulation is receptor desensitization. This phenomenon can be experimentally demonstrated in the set-up depicted in Figure 9.7 Stimulating electrodes produce presynaptic action potentials, which induce release of acetylcholine into the synaptic cleft. Acetylcholine will trigger postsynaptic action potentials, which in turn are de-... 

---