Optimum concentration–response curve metrics for supervised selection of discriminative cellular phenotypic endpoints for chemical hazard assessment

The EYTEX® system has been shown to be a very useful tool in the in vitro testing of toiletry raw materials. However, the interpretation of the results is not always simple. It requires an understanding of the physicochemical characteristics of the samples and of their interactions with components of the EYTEX® system. The results of 364 assays using the EYTEX® standard assay, membrane partition assay, rapid membrane assay and upright membrane assay protocols have been collated against the problem areas for each method. These assays were performed on a collection of 18 pure surfactant raw materials and also on blends of surfactants. The results for 18 surfactants are reviewed according to surfactant type and interpreted with reference to the concentration-response curve for each material. This paper describes the problem areas of inhibition, interference and negative optical densities associated with the non-qualification of EYTEX® assays, and shows how they have been overcome. In conclusion, some guidelines for using a concentration-response assay are given, so that the optimum concentration for a dose-response assay for a new sample can be obtained with the minimum waste of time or reagents.

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Epigenetic biomarkers as tools for chemical hazard assessment: Gene expression profiling using the model Danio rerio

The Science of The Total Environment ◽

10.1016/j.scitotenv.2020.144830 ◽

2021 ◽

Vol 773 ◽

pp. 144830

Author(s):

Tiago Torres ◽

Raquel Ruivo ◽

Miguel Machado Santos

Keyword(s):

Gene Expression ◽

Gene Expression Profiling ◽

Hazard Assessment ◽

Danio Rerio ◽

Expression Profiling ◽

Epigenetic Biomarkers ◽

Chemical Hazard

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Cholinergic stimulation modulates negative inotropic effect of cocaine on ferret ventricular myocardium

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.270.2.h678 ◽

1996 ◽

Vol 270 (2) ◽

pp. H678-H684

Author(s):

L. Miao ◽

Z. Qiu ◽

J. P. Morgan

Keyword(s):

Response Curve ◽

Negative Inotropic Effect ◽

Ventricular Myocardium ◽

Inotropic Effect ◽

Dependent Manner ◽

Cholinergic Stimulation ◽

Concentration Dependent Manner ◽

Cell Shortening ◽

Inotropic State ◽

Concentration Response Curve

We tested the hypothesis that the negative inotropic effect (NIE) of cocaine is mediated, at least in part, by cholinergic stimulation and can be correlated with the degree of adenosine 3',5'-cyclic monophosphate (cAMP) dependency of the inotropic state. Cardiac myocytes were isolated from left ventricles of ferrets and loaded with the fluorescent Ca2+ indicator indo 1. Cells were placed in physiological solution containing 2.0 mM Ca2+ and stimulated at 0.5 Hz and 30 degrees C. Cocaine decreased peak cell shortening and peak intracellular Ca2+ in a concentration-dependent manner (10(-8)-10(-4) M). The concentration-response curve of cocaine was shifted significantly downward compared with those of lidocaine and procaine in the same range of concentrations. Atropine (10(-6) M) shifted the concentration-response curve of cocaine, but not those of lidocaine and procaine, rightward, with a pA2 value (7.66) similar to that obtained with carbachol (7.99). With prior addition of isoproterenol (ISO, 10(-8) M) or increased Ca2+ (4.0 mM) to increase cell shortening to the same degree (approximately 60%), cocaine and carbachol decreased contractility to a significantly greater extent in ISO-stimulated myocytes. To clarify whether these treatments changed responsiveness of the contractile elements to Ca2+, the effect of 2,3-butanedione monoxime, an agent that interferes with the interaction of myosin and actin, was tested with previous addition of ISO or increased Ca2+, and no differential effect occurred. Therefore, we postulate that 1) the NIE of cocaine on myocytes is caused by decreased Ca2+ availability; 2) this effect is due to specific stimulation of cholinergic receptors in addition to other direct myocardial (probably local anesthetic) effects; and 3) the NIE correlates with the level of cAMP dependence of the inotropic state.

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Agonist Efficiency Estimated from Concentration Response Curve

Biophysical Journal ◽

10.1016/j.bpj.2020.11.577 ◽

2021 ◽

Vol 120 (3) ◽

pp. 57a

Author(s):

Dinesh Indurthi ◽

Anthony Auerbach

Keyword(s):

Response Curve ◽

Concentration Response Curve

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The Cellular Prion Protein Prevents Copper-Induced Inhibition of P2X4Receptors

International Journal of Alzheimer s Disease ◽

10.4061/2011/706576 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6

Author(s):

Ramón A. Lorca ◽

Lorena Varela-Nallar ◽

Nibaldo C. Inestrosa ◽

J. Pablo Huidobro-Toro

Keyword(s):

Amino Acids ◽

Synaptic Transmission ◽

Prion Protein ◽

Adenosine Triphosphate ◽

Response Curve ◽

Physiological Function ◽

Cellular Prion Protein ◽

Synaptic Activity ◽

Receptor Subtype ◽

Concentration Response Curve

Although the physiological function of the cellular prion protein (PrPC) remains unknown, several evidences support the notion of its role in copper homeostasis. PrPCbinds Cu2+through a domain composed by four to five repeats of eight amino acids. Previously, we have shown that the perfusion of this domain prevents and reverses the inhibition by Cu2+of the adenosine triphosphate (ATP)-evoked currents in the P2X4receptor subtype, highlighting a modulatory role for PrPCin synaptic transmission through regulation of Cu2+levels. Here, we study the effect of full-length PrPCin Cu2+inhibition of P2X4receptor when both are coexpressed. PrPCexpression does not significantly change the ATP concentration-response curve in oocytes expressing P2X4receptors. However, the presence of PrPCreduces the inhibition by Cu2+of the ATP-elicited currents in these oocytes, confirming our previous observations with the Cu2+binding domain. Thus, our observations suggest a role for PrPCin modulating synaptic activity through binding of extracellular Cu2+.

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gamma-Aminobutyric acid-induced response in rat dissociated paratracheal ganglion cells

Journal of Neurophysiology ◽

10.1152/jn.1992.67.5.1367 ◽

1992 ◽

Vol 67 (5) ◽

pp. 1367-1374 ◽

Cited By ~ 12

Author(s):

S. Itabashi ◽

K. Aibara ◽

H. Sasaki ◽

N. Akaike

Keyword(s):

Response Curve ◽

Ganglion Cells ◽

Aminobutyric Acid ◽

Equilibrium Potential ◽

Induced Response ◽

Dependent Manner ◽

Gamma Aminobutyric Acid ◽

Patch Clamp Technique ◽

Concentration Dependent Manner ◽

Concentration Response Curve

1. The pharmacologic properties of gamma-aminobutyric acid (GABA)-induced Cl- current (ICl) were studied in the paratracheal ganglion cells freshly dissociated from 7- to 10-day-old rat trachea in a whole-cell recording mode by the use of a conventional patch-clamp technique. 2. GABA- and muscimol-induced currents increased sigmoidally in a concentration-dependent manner, and both currents reversed at approximately -3 mV, which was close to the Cl- equilibrium potential (ECl). 3. Strychnine (STR) at low concentration and bicuculline (BIC) inhibited GABA response competitively, whereas STR at the higher concentrations, benzylpenicillin (PCG), or picrotoxin (PTX) inhibited noncompetitively. Inhibition of GABA response by PCG but not other antagonists was voltage dependent, indicating that PCG acts as a Cl- channel blocker. 4. The concentration-response curve of pentobarbital sodium (PB)-induced ICl was bell shaped. At concentrations higher than 10(-3) M, both the peak and plateau currents decreased, and a transient "hump" current appeared immediately after washing out PB. In the presence of PB, the concentration-response curve of GABA shifted toward left without changing the maximum response. 5. Although diazepam (DZP) at concentration used did not induce a response, it potentiated the GABA response in a concentration-dependent manner between 10(-8) and 10(-6) M. DZP also caused a parallel shift toward left in the concentration-response curve of GABA. 6. PB or DZP further enhanced the GABA response in the presence of the other agent. 7. It is concluded that the properties of GABAA receptors in the paratracheal ganglion cells are essentially similar to those reported in other preparations.

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