Receptor availability

Receptor occupancy refers to the ratio of receptors occupied by a ligand at equilibrium and the total number of receptors available, usually expressed as a percentage of the total number of receptors. Since it is often not possible to quantify the total number of receptors or the number of receptors occupied by a ligand, another parameter called binding potential is often used to measure receptor occupancy. Binding potential (BP) refers to the ratio of the maximum number of receptors and the equilibrium dissociation constant of the drug, so that % receptor occupancy equals to... 

Staley, J., Krishnan-Sarin, S., Cosgrove, K. et al. P2 Nicotinic acetylcholine receptor availability in recently abstinent smokers. J. Neurosci. Accepted. 

Wang, G.J., Volkow, N.D., Fowler, J.S. et al. Dopamine D2 receptor availability in opiate-dependent subjects before and after naloxone-precipitated withdrawal. Neuropsychopharmacology. 16 174, 1997. 

Addition of 81-SH to 80-SS-81 led to formation of the homodisulfide compounds and an equilibrium, with an exchange constant of 1.8, was established. The presence of the templating (D)Pro(L)Val(D)Val tri-peptide in this mixture, shifted the equilibrium dramatically and the formation of the homodisulfide 80-SS-80 was amplified with a Keq=32. Since the templating tri-peptide was supported on polymer beads, the isolation of receptor 80-SS-80 (in 97% purity) was achieved easily by extraction of the beads. The formation of multiple hydrogen bonds between the template and the components of the DCL, led to the isolation of the best possible receptor available from the building blocks present in the equilibrated mixture. 

Volkow ND, Fowler JS, Wang GJ, Hitzemann R, Logan J, Schlyer DJ, Dewey SL, Wolf AP. (1993). Decreased dopamine D2 receptor availability is associated with reduced frontal metabolism in cocaine abusers. Synapse. 14(2) 169-77. 

Wtkipedia.com."Opioid Receptors. Available online at http //en.wildpedia.org/ wild/Opioid receptor. Accessed June 2,2006. 

Receptor down-regulation is a phenomenon whereby an agonist, after binding to a receptor, acmally induces a decrease in the number of those receptors available for binding. Receptor up-regulation is the opposite and involves an agonist-induced increase in the number of receptors. 

The number of receptor sites and the position of the equilibrium (Eq. 1) as reflected in KT, will clearly influence the nature of the dose response, although the curve will always be of the familiar sigmoid type (Fig. 2.4). If the equilibrium lies far to the right (Eq. 1), the initial part of the curve may be short and steep. Thus, the shape of the dose-response curve depends on the type of toxic effect measured and the mechanism underlying it. For example, as already mentioned, cyanide binds very strongly to cytochrome a3 and curtails the function of the electron transport chain in the mitochondria and hence stops cellular respiration. As this is a function vital to the life of the cell, the dose-response curve for lethality is very steep for cyanide. The intensity of the response may also depend on the number of receptors available. In some cases, a proportion of receptors may have to be occupied before a response occurs. Thus, there is a threshold for toxicity. With carbon monoxide, for example, there are no toxic effects below a carboxyhemoglobin concentration of about 20%, although there may be... 

And why is it that, while we could evoke these enzymes by cortisol (e.g. alanine aminotransferase) or thyroxine (malic enzyme) in neonatal life, we could not do so prenatally The explanation can clearly cannot lie in receptor availability since the same hormones do induce alternative enzymes at the same fetal stage. 

Beyond delta agonist selectivity and mu or delta receptor availability in vivo, the observation of decreased delta agonist efficacy in mice lacking mu receptors could also be explained by functional cooperation of mu and delta receptors. It is likely that some delta receptor-mediated effects require mu receptors for full activity (see Rothman and Xu, Chap. 21). Where in the brain, and whether this occurs between receptors located in the same neurons or on different neurons within neural circuits, remains to be determined. 

Raedler TJ. 2007a. Comparison of the in vivo muscarinic cholinergic receptor availability in patients treated with clozapine and olanzapine. Int J Neuropsychopharmacol 10 275-280. 

Raedler TJ, Knable MB, Jones DW, Urbina RA, Egan MF, et al. 2003a. Central muscarinic acetylcholine receptor availability in patients treated with clozapine. Neuropsychopharmacol 28 1531-1537. 

In vivo the PET studies have revealed that low D2 receptor availability is a common feature of many drugs of abuse, e.g. cocaine (Volkow et al., 1990, 1997),... 

Parsey RV, Oquendo MA, Zea-Ponce Y, Rodenhiser J, Kegeles LS, Pratap M, Cooper TB, Van Heertum R, Mann JJ, Laruelle M (2001) Dopamine D2 receptor availability and amphetamine-induced dopamine release in unipolar depression. Biol Psychiatry 50 313-322. 

Pohjalainen T, Rinne JO, Nagren K, Lehikoinen P, Anttila K, Syvalahti EK, Hietala J (1998) The A1 allele of the human D2 dopamine receptor gene predicts low D2 receptor availability in healthy volunteers. Mol Psychiatry 3 256—260. 

Schlyer DJ, Dewey SL, Wolf AP. Decreased dopamine D2 receptor availability is associated with reduced frontal 154. 

Nuclear Receptor Signaling Atlas. A web sited aimed at developing a comprehensive understanding of the structure, function, and role in disease of nuclear receptors. Available at http //www.nursa.org/ index, cfm. 

The cellular interaction of agonists depends on the physico-chemical nature and on the topographical distribution of the membrane receptors (62). Thus thrombin and PGE, mediated responses would depend on the number and the type (high affinity/low affinity) of receptors available for interaction with thrombin or PGE, respectively. The possibility diat platelets fiwrn SHR exhibit greater sensitivity to thrombin and PGE, because of differences in munber or affinity of their respective receptors has been examined by us (23,24). Hirombin as well as PGE, binding sites/platelets and dissociation constants have been found to be similar in WKY and SHR platelets (Fig.7, ref 23,24). Therefore, increased platelet reactivity to thrombin or PGE, is not attributable to changes in the number or the affinity of their respective receptors. 

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