Mechanisms receptors

Fig. 21. (a) Diagrammatical representation of an allosteric receptor mechanism (b) allosteric binding of a thymine derivative promoted on uptake (34). 

Ah-receptor-mediated toxicity is particularly associated with the highly toxic compound 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD), commonly referred to as dioxin. TCDD, and the concept of toxicity equivalency factors (TEFs) based on TCDDs, will be dealt with in Chapter 7. The main point to make at this juncture is that the toxicity of each individual coplanar congener in a mixture can be expressed in terms of a toxic equivalent calculated relative to the toxicity of dioxin. Summation of the toxic equivalents of the individual coplanar PCBs gives a measure of the toxicity of the whole mixture, as expressed through the Ah receptor mechanism. 

Davis A, Perkins M The involvement of bradykinin B1 and B2 receptor mechanisms in cytokine-induced mechanical hyperalgesia in the rat. Br J Pharmacol 1994 113 63-68. 

Thus the activity of a neuron can be controlled in a number of ways by NTs activating appropriate receptors (Fig. 1.5). Two basic receptor mechanisms are involved ... 

Figure 12.2 A hypothetical synapse where co-existence of peptides and classical transmitters occurs. A is a classical transmitter whereas B and C are peptides. The slow synthesis of peptides and the need for axonal transport may mean that in active neurons, the classical transmitter may be released under all conditions, but the peptide(s) may require higher intensities of stimulation for release and be depleted if the neuron continues to fire for long periods. Competition for peptidases can lead to changes in levels of two co-released peptides. At the postsynaptic site, the receptor mechanisms of the co-existing transmitters can also produce complex changes in neuronal activity...

Loh HH, Law PY. The role of membrane lipids in receptor mechanisms. Annu Rev Pharmacol Toxicol 1980 20 201-234. 

This chapter deals mainly with information that can be obtained from equilibrium, or at least steady-state, recordings of ion-channel receptor activity. However, a great deal of information has also been obtained from kinetic studies of ion channels where the aim has been to determine values for the rate constants in a receptor mechanism. In general, only equilibrium constants can be determined from equilibrium studies. 

Changes in the occupancy of the open-channel state of the receptor as a function of time (pA2R (t)) in response to a perturbation of the receptor equilibrium can be used to obtain information about the rates of channel gating and the interaction of dmgs with ion-channel receptors. The system is said to relax towards a new equilibrium. The time course of the relaxation is used to measure rates from the average behavior of many ion channels in a recording, while noise analysis uses the frequency of the moment-to-moment fluctuations in occupancy of the open-channel state at equilibrium to provide information about the rates in the receptor mechanism. 

EEG slow waves. The differential EEG and ACh responses to dialysis delivery of AF-DX 116 (M2/M4) versus pirenzepine (M1/M4) supports the conclusion that, in B6 mouse, postsynaptic muscarinic receptors of the Ml subtype form one receptor mechanism by which ACh activates the EEG (Douglas et al, 2002a). The data summarized in Fig. 5.11 provide direct measures of G protein activation in basal forebrain and prefrontal cortex by muscarinic cholinergic receptors (DeMarco et al, 2004). The in vitro data of Fig. 5.11A indicate the presence of functional muscarinic receptors in regions of B6 mouse prefrontal cortex where in vivo microdialysis studies (Douglas et al, 2002a, b) revealed modulation of ACh release and EEG by pre- and postsynaptic muscarinic receptors (Figs. 5.9 and 5.10). 

Amici, R., Sanford, L. D., Kearney, K. et al. (2004). A serotonergic (5-HT2) receptor mechanism in the laterodorsal tegmental nucleus participates in regulating the pattern of rapid-eye-movement sleep occurrence in the rat. Brain Res. 996, 9-18. 

Na+,H+ antiporters (NHE) occur in synaptosomes, glia and neuroblastoma cells [60] (Fig. 5-8B). They are relatively inactive at neutral pH but with a decrease in intracellular pH they produce an efflux of protons at the expense of the Na+ gradient. The NHE transport stoichiometry is 1 1. Activation by an internal pH decrement apparently results from protonation of a cytoplasmic site, which allosterically increases the affinity of the proton ionophoric site. In some cells, the NHE is under additional control by receptor mechanisms. Several growth factors and hormones produce transient cytoplasmic alkalinization, probably by mediating a protein kinase... 

Fas ligand and interleukin-ip), the neurotransmitter glutamate and thrombin. Like tumor necrosis factor (TNF) receptors, Fas is coupled to downstream death effector proteins that ultimately induce caspase activation (Ch. 22). Fas and TNF receptors recruit proteins called FADD and TRADD respectively FADD and TRADD then activate caspase-8, which, in turn, activates caspase-3 (Fig. 35-4). Calcium ion influx mediates neuronal apoptosis induced by glutamate receptor activation calcium induces mitochondrial membrane permeability transition pore opening, release of cytochrome c and caspase activation. Interestingly, in the absence of neurotrophic factors some neurotrophic factor receptors can activate apoptotic cascades, the low-affinity NGF receptor being one example of such a death receptor mechanism [23],... 

This drug has marked immunomodulatory effects and can alter the normal function of T and B lymphocytes, NK cells and macrophages, both in vivo and in vitro, in humans and animals (Table 30.1).910 Although the molecular and cellular mechanisms for these effects are not fully defined, it is believed that both receptor and non-receptor mechanisms are involved. Cannabinoid receptors (CBRs) are G-protein coupled 7-... 

Together, all the inferences from both computational modeling and simulation (which can reveal novel aspects of the receptor mechanisms, based on the dynamic properties of the proteins) serve as mechanistic working hypotheses for new and more focused experiments. This mode of closely considered interactions and synergy between computational developments and experimental probing of the receptor systems has become a sustained characteristic of current studies of structure-function... 

Stewart, M. R., Campbell, A., Sperk, G., and Baldessarini, R. J. (1979) Receptor mechanisms in increased sensitivity to serotonin agonists after dihydroxytryptamine shown by electronic monitoring of muscle twitches in the rat. Psychopharmacology, 60 281-289. 

Gorodeski GI [2002] Regulation of transcervical permeability by two distinct P2-purinergic receptor mechanisms. Am J Physiol 282 C75-C83... 

Zarrindast MR, Pazouki M, Nassiri-Rad S. (1997). Involvement of cholinergic and opioid receptor mechanisms in nicotine-induced antinociception. Pharmacoi Toxicoi. 81(5) 209-13. 

Zinkand WC, Moore WC, Thompson C, Salama AI, Patel J. (1992). Ibotenic acid mediates neurotoxicity and phosphoinositide hydrolysis by independent receptor mechanisms. Mol Chem Neuropathol. 16(1-2) 1-10. 

Talhout R, Opperhuizen A, van Amsterdam JG (2007) Role of acetaldehyde in tobacco smoke addiction, Eur Neuropsychopharmacol 17 627-636 Tanda G, Pontieii FE, Di Chiara G (1997) Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common mul opioid receptor mechanism. Science 276 2048-2050 Taylor JR, Robbins TW (1984) Enhanced behavioural control by conditioned reinforcers following microinjections of d-amphetamine into the nucleus accumbens. Psychopharmacology 84 405 12... 

Thus drug discrimination can serve as an in vivo surrogate assay for receptor activation where the cne is selective for a particular receptor. It is a selective and sensitive in vivo measnre of nenronal and receptor mechanisms and can help researchers to understand more of the brain s fundamental processes. It is the only assay allowing a direct test in which subjects that do not have language (e.g. rodents) can detect the presence of a psychoactive substance in the body and define the extent of the similarity of its effects to those of other substances. 

Murrayaquinone A (107) (see Scheme 2.21) was found to produce a triphasic inotropic response of guinea-pig papillary muscle. This triphasic inotropic response is not mediated through a receptor mechanism, but through a mechanism involving ATP production (473). 

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