The binding of physostigmine to human serum albumin

Whelpton, Robin; Hurst, Philip

doi:10.1111/j.2042-7158.1990.tb07027.x

Cited by 9 publications

(8 citation statements)

References 11 publications

(13 reference statements)

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“…Studies have also suggested that the esterase-like activity of serum albumin could result from a contamination by butyrylcholinesterase or other esterases (37,38). At present, it is not clear whether the esterase activity of albumin is intrinsic to the protein or due to the presence of an esterase impurity.…”

Section: Discussionmentioning

confidence: 90%

Ghrelin Interacts with Human Plasma Lipoproteins

et al. 2007

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Ghrelin, a peptide hormone produced predominantly by the stomach, stimulates food intake and GH secretion. The Ser 3 residue of ghrelin is mainly modified by a n-octanoic acid. In the human bloodstream, ghrelin circulates in two forms: octanoylated and desacylated. We previously demonstrated that ghrelin is desoctanoylated in human serum by butyrylcholinesterase (EC 3.1.1.8) and other esterase(s), whereas in rat serum, only carboxylesterase (EC 3.1.1.1) is involved. The aims of this study were to determine the role of lipoprotein-associated enzymes in ghrelin desoctanoylation and the role of lipoproteins in the transport of circulating ghrelin. Our results show that ghrelin desoctanoylation mostly occurred in contact with low-density lipoproteins (LDLs) and lipoproteinpoor plasma subfractions. Butyrylcholinesterase and platelet-activating factor acetylhydrolase (EC 3.1.1.47) were responsible for the ghrelin hydrolytic activity of the lipoproteinpoor plasma and LDL subfractions, respectively. Moreover, we observed that ghrelin is associated with triglyceride-rich lipoproteins (TRLs), high-density lipoproteins (HDLs), very high-density lipoproteins (VHDLs), and to some extent LDLs. In conclusion, we report that the presence of the acyl group is necessary for ghrelin interaction with TRLs and LDLs but not HDLs and VHDLs. Ghrelin interacts via its N-and C-terminal parts with HDLs and VHDLs. This suggests that, whereas TRLs mostly transport acylated ghrelin, HDLs and VHDLs transport both ghrelin and des-acyl ghrelin. (Endocrinology 148: [2355][2356][2357][2358][2359][2360][2361][2362] 2007)

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Section: Discussionmentioning

confidence: 90%

Ghrelin Interacts with Human Plasma Lipoproteins

et al. 2007

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“…It is important to note that the organophosphates show strong binding to serum proteins both in vivo and in vitro (Braeckman et al 1983; Qiao et al 2001), which reduces their bioeffective concentrations. The effect is highest for chlorpyrifos, less important for parathion, even lower for diazinon, and lowest for physostigmine (Braeckman et al 1983; Sultatos et al 1984; Whelpton and Hurst 1990; Wu et al 1996). For the present study, serum proteins could not be deleted from the medium because they are required to maintain cell growth and viability, and consequently, the rank order of effects changes so that diazinon and physostigmine, with their lower binding, exert greater net effects than would otherwise be expected.…”

Section: Discussionmentioning

confidence: 99%

Screening for Developmental Neurotoxicity Using PC12 Cells: Comparisons of Organophosphates with a Carbamate, an Organochlorine, and Divalent Nickel

Slotkin

MacKillop

Ryde

et al. 2007

Environ Health Perspect

117

191

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BackgroundIn light of the large number of chemicals that are potential developmental neurotoxicants, there is a need to develop rapid screening techniques.ObjectivesWe exposed undifferentiated and differentiating neuronotypic PC12 cells to different organophosphates (chlorpyrifos, diazinon, parathion), a carbamate (physostigmine), an organochlorine (dieldrin), and a metal (divalent nickel; Ni2+) and examined indices of cell replication and differentiation for both short- and long-term exposures.ResultsIn undifferentiated cells, all the agents inhibited DNA synthesis, with the greatest effect for diazinon, but physostigmine eventually produced the largest deficits in the total number of cells after prolonged exposure. The onset of differentiation intensified the adverse effects on DNA synthesis and changed the rank order in keeping with a shift away from noncholinergic mechanisms and toward cholinergic mechanisms. Differentiation also worsened the effects of each agent on cell number after prolonged exposure, whereas cell growth was not suppressed, nor were there any effects on viability as assessed with trypan blue. Nevertheless, differentiating cells displayed signs of oxidative stress from all of the test compounds except Ni2+, as evidenced by measurements of lipid peroxidation. Finally, all of the toxicants shifted the transmitter fate of the cells away from the cholinergic phenotype and toward the catecholaminergic phenotype.ConclusionsThese studies point out the feasibility of developing cell-based screening methods that enable the detection of multiple end points that may relate to mechanisms associated with developmental neurotoxicity, revealing some common targets for disparate agents.

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“…Physostigmine is bound to serum proteins although estimates of binding affinity and capacity differ markedly (243,264,282). In rat plasma, physostigmine binding decreased slightly from 49% to 41% with increasing physostigmine concentration over a 50-fold range from 0.16 to 8.1 nmolml, whereas binding increased in human plasma from 29% to 43% over the same concentration range.…”

Section: Binding To Plasma Proteinsmentioning

confidence: 90%

“…The binding of physostigmine to human serum albumin has been characterized by Whelpton and Hurst (282). Over the concentration range 3.3 nM to 2.7 µM, a single class of binding sites was determined with an affinity constant of 8 × 10 7 lmol and a density of approximately 3 nM.…”

Section: Binding To Plasma Proteinsmentioning

confidence: 99%