Why is there no morphine concentration-response curve for acute pain?

2014 ◽  
Vol 24 (3) ◽  
pp. 233-238 ◽  
Author(s):  
Brian J Anderson ◽  
John van den Anker
Keyword(s):  
Acute Pain ◽  
Response Curve ◽  
Morphine Concentration ◽  
Concentration Response Curve

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

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.

scholarly journals Agonist Efficiency Estimated from Concentration Response Curve

2021 ◽  
Vol 120 (3) ◽  
pp. 57a
Author(s):  
Dinesh Indurthi ◽  
Anthony Auerbach
Keyword(s):  
Response Curve ◽  
Concentration Response Curve

scholarly journals The Cellular Prion Protein Prevents Copper-Induced Inhibition of P2X4Receptors

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+.

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

1992 ◽  
Vol 67 (5) ◽  
pp. 1367-1374 ◽  
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.

Renal microvascular effects of endothelin

1990 ◽  
Vol 259 (2) ◽  
pp. F217-F221 ◽  
Author(s):  
R. M. Edwards ◽  
W. Trizna ◽  
E. H. Ohlstein
Keyword(s):  
Response Curve ◽  
Contractile Response ◽  
Maximum Response ◽  
Lumen Diameter ◽  
Rabbit Kidney ◽  
Significant Shift ◽  
Efferent Arteriole ◽  
Endothelin 1 ◽  
Afferent Arterioles ◽  
Concentration Response Curve

The effects of endothelin 1, 2, and 3 (ET-1, -2, -3) on lumen diameter of individual afferent and efferent arterioles dissected from rabbit kidney were examined. ET-1 produced concentration-dependent and long-lasting decreases in lumen diameter in both arterioles. The 50% maximum response (EC50) values were 1.4 +/- 0.41 and 0.9 +/- 0.65 nM for afferent and efferent arterioles, respectively. In afferent arterioles, ET-2 produced decreases in lumen diameter (EC50 = 3.3 +/- 1.75 nM) that were indistinguishable from ET-1. However, ET-3 was considerably less potent (EC50 = 21.9 +/- 6.0 nM, P less than 0.05) than ET-1 or ET-2. Similar results were obtained in the efferent arteriole in which the EC50 for ET-2 (0.25 +/- 0.1 nM) was similar to ET-1, but ET-3 was significantly less potent (EC50 = 2.6 +/- 0.4 nM, P less than 0.05). Nicardipine (0.01-1 microM) produced concentration-dependent shifts in the ET-1 concentration-response curve in afferent arterioles. Verapamil (1 microM) also caused a significant shift in the ET-1 response curve. The contractile response to ET-1 was significantly more sensitive to nicardipine than was the response to norepinephrine. In contrast, the response of efferent arterioles to ET-1 and norepinephrine was unaffected by nicardipine or verapamil. The results demonstrate that ETs are potent vasoconstrictors of both the pre- and postglomerular microvasculature and may play a role in the regulation of renal hemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS)

Superoxide anion impairs Ca2+mobilization in cultured human nasal epithelial cells

1999 ◽  
Vol 277 (6) ◽  
pp. L1089-L1095
Author(s):  
Tetsuya Koyama ◽  
Masahiro Oike ◽  
Sohtaro Komiyama ◽  
Yushi Ito
Keyword(s):  
Superoxide Dismutase ◽  
Epithelial Cells ◽  
Superoxide Anion ◽  
Response Curve ◽  
Krebs Solution ◽  
Nasal Epithelial Cells ◽  
Human Nasal Epithelial Cells ◽  
Bath Application ◽  
Intracellular Ca ◽  
Concentration Response Curve

We examined the effects of superoxide anion ([Formula: see text]) on the intracellular Ca2+ concentration in cultured human nasal epithelial cells. The cells were exposed to[Formula: see text] by pretreatment with xanthine (X) and xanthine oxidase (XO); control cells were treated with X alone. When Ca2+-containing Krebs solution was reperfused in the thapsigargin-treated, store-depleted cells, reapplication-induced intracellular Ca2+ concentration elevation was significantly smaller in X/XO-treated cells than in the control cells, suggesting that [Formula: see text] impairs Ca2+ release-activated Ca2+ entry (CRAC). Bath application of ATP induced a steep Ca2+ transient in both control and X/XO-treated cells. However, the concentration-response curve of the ATP-induced Ca2+ transient was shifted to a higher concentration in X/XO-treated cells. The impairments of CRAC and ATP-induced Ca2+ transient induced by X/XO were reversed by superoxide dismutase. Furthermore, all these X/XO-induced effects were also observed in cells pretreated with pyrogallol, also an [Formula: see text] donor. These results indicate that [Formula: see text] impairs at least two mechanisms involved in Ca2+ mobilization in human nasal epithelial cells, i.e., CRAC and ATP-induced Ca2+ release.

scholarly journals Characterization of the concentration-response curve for ambient ozone and acute respiratory morbidity in 5 US cities

2018 ◽  
Vol 29 (2) ◽  
pp. 267-277 ◽  
Author(s):  
Vaughn Barry ◽  
Mitchel Klein ◽  
Andrea Winquist ◽  
Howard H. Chang ◽  
James A. Mulholland ◽  
...  
Keyword(s):  
Response Curve ◽  
Respiratory Morbidity ◽  
Ambient Ozone ◽  
Us Cities ◽  
Concentration Response Curve

scholarly journals Effects of substance P on identified neurons of the rat dorsal motor nucleus of the vagus

2001 ◽  
Vol 281 (1) ◽  
pp. G164-G172 ◽  
Author(s):  
Mark W. Lewis ◽  
R. Alberto Travagli
Keyword(s):  
Substance P ◽  
Response Curve ◽  
Target Organ ◽  
Motor Nucleus ◽  
Peripheral Target ◽  
Previous Evidence ◽  
Dorsal Motor Nucleus ◽  
Whole Cell Patch Clamp ◽  
Neuronal Groups ◽  
Concentration Response Curve

Previous evidence suggests that substance P (SP) activates subpopulations of neurons within the dorsal motor nucleus of the vagus (DMV). In this study we aimed at identifying these subpopulations in relation to their gastrointestinal projection organs or vagal branches and characterizing pharmacologically the SP response. Using whole cell patch-clamp recordings from identified gastrointestinal-projecting vagal motoneurons, we found that SP induced an inward current in all neuronal groups except for cecum-projecting cells. The lowest percentage of SP-responding neurons was found in fundus-projecting cells, where SP also had a concentration-response curve that was shifted to the left ( P < 0.05). Independently from the projections, the SP response was reduced by sendide and MEN 10,376 and mimicked by a combination of [Sar9-Met(O2)11]SP and α-neurokinin. SP and α-neurokinin also increased the frequency, but not the amplitude, of postsynaptic currents. In conclusion, we demonstrated that SP induces both pre- and postsynaptic effects on DMV neurons via activation of neurokinin NK1 and NK2 receptors. The magnitude of the SP response was correlated to the peripheral target organ.

Allosteric modulation of GABAA receptors in acutely dissociated neurons of the suprachiasmatic nucleus

1996 ◽  
Vol 270 (6) ◽  
pp. C1726-C1734 ◽  
Author(s):  
M. Shimura ◽  
N. Harata ◽  
M. Tamai ◽  
N. Akaike
Keyword(s):  
Gabaa Receptor ◽  
Suprachiasmatic Nucleus ◽  
Gabaa Receptors ◽  
Response Curve ◽  
Equilibrium Potential ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Gabaa Receptor Antagonist ◽  
Inward Currents ◽  
Concentration Response Curve

The gamma-aminobutyric acid (GABA)-induced response was investigated in acutely dissociated suprachiasmatic nucleus (SCN) neurons of 11- to 14-day-old rats, under the voltage-clamp condition of nystatin-perforated patch recording. At a holding potential of -40 mV, application of GABA induced inward currents in a concentration-dependent manner. Pentobarbital and 5 beta-pregnan-3 alpha-ol-20-one (pregnanolone) similarly induced inward currents. GABA-induced inward currents were suppressed in a concentration-dependent manner by pretreating neurons with a GABAA receptor antagonist, bicuculline. Bicuculline (3 x 10(-6) M) shifted the concentration-response curve of GABA to the left in a competitive manner. Reversal potential of the GABA response (EGABA) was -3.4 +/- 0.7 mV, close to the theoretical Cl- equilibrium potential of -4.1 mV. Pretreating SCN neurons with diazepam, pentobarbital, and pregnanolone enhanced the 3 x 10(-6) M GABA response. Diazepam (3 x 10(-8) M), pentobarbital (3 x 10(-5) M), and pregnanolone (10(-7) M) shifted the concentration-response curve of GABA to the left without changing the maximal amplitude of GABA responses. EGABA in the presence of diazepam, pentobarbital, or pregnanolone was the same as that in their absence. These results show that the GABA response in acutely dissociated SCN neurons is mediated by the GABAA receptor. Because the GABAA receptor of SCN neurons is allosterically augmented by diazepam, pentobarbital, and pregnanolone, similarly as in other regions of the central nervous system, the present study opens up ways to functionally modulate the GABAA receptors in SCN.

Comparison of Five Experimental Pain Tests to Measure Analgesic Effects of Alfentanil

2001 ◽  
Vol 95 (1) ◽  
pp. 22-29 ◽  
Author(s):  
Martin Luginbühl ◽  
Thomas W. Schnider ◽  
Steen Petersen-Felix ◽  
Lars Arendt-Nielsen ◽  
Alex M. Zbinden
Keyword(s):  
Response Curve ◽  
Plasma Concentrations ◽  
Experimental Pain ◽  
Pain Tolerance ◽  
Time Effect ◽  
Intraindividual Variation ◽  
Pressure Pain ◽  
Pain Tests ◽  
Ice Water ◽  
Concentration Response Curve

Background Several experimental pain models have been used to measure opioid effects in humans. The aim of the current study was to compare the qualities of five frequently used experimental pain tests to measure opioid effects. Methods The increase of electrical, heat, and pressure pain tolerance and the decrease of ice-water and ischemic pain perception was determined at baseline and at four different plasma concentrations of alfentanil (n = 7) administered as target controlled infusion or placebo (n = 7). A linear mixed-effects modeling (NONMEM) was performed to detect drug, placebo, and time effect as well as interindividual and intraindividual variation of effect. Results Only the electrical, ice-water, and pressure pain tests are sensitive to assess a concentration-response curve of alfentanil. At a plasma alfentanil concentration of 100 ng/ml, the increase in pain tolerance compared with baseline was 42.0% for electrical pain, 22.2% for pressure pain, and 21.7% for ice-water pain. The slope of the linear concentration-response curve had an interindividual coefficient of variation of 58.3% in electrical pain, 35.6% in pressure pain, and 60.0% in ice-water pain. The residual error including intraindividual variation at an alfentanil concentration of 100 ng/ml was 19.4% for electrical pain, 6.1% for pressure pain, and 13.0% for ice-water pain. Electrical pain was affected by a significant placebo effect, and pressure pain was affected by a significant time effect. Conclusion Electrical, pressure, and ice-water pain, but not ischemic and heat pain, provide significant concentration-response curves in the clinically relevant range of 200 ng/ml alfentanil or lower. The power to detect a clinically relevant shift of the curve is similar in the three tests. The appropriate test(s) for pharmacodynamic studies should be chosen according to the investigated drug(s) and the study design.

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