Concentration-Effect Curves for Histamine-Induced Effect of Guinea-Pig Ileum - Lab Report Example

BIOLOGY Your name Name of Assignment 14th March, 2013 Concentration-effect curves for histamine-induced effect of guinea-pig ileum in the presence and absence of the concentrations of mepyramine 1X10-9 From the concentration-effect curves, the dose that is necessary to produce a response that is equal 50% of the maximum response induced values for mepyramine were determined to be 1.25x10-6. This means that the maximum response produced by histamine was depressed thus it means they were ineffective. It is important in order to reduce the negative effects caused by the histamine at these levels. This concentration is one of the most effective long-term measures of dosage usage. The ED50 values for mepyramine after histamine-induced effect of guinea-pig ileum of 1X10-9. Maximal contractions induced by the histamine-induced was using mean + standard error of the mean. At 1X10-9 the response produced histamine was not significant although there is inducement of short circuit current. The main response non effectiveness of mepyramine is because histamine was blocked. Histamine influences mepyramine exchange process thus acting as a receptors This supported by constant oscillation of the curve up and down as the concentration changes. Then calculate equipotent concentration ratios (ECR)- this is where molar concentration of Histamine is divided by mepyramine at point where a response is equal 50% of the maximum response induced values for mepyramine Equipotent concentration ratio = = 12.5 Conc Histamine Mepyramine 1 x 10-9 M ECR the log of the (ECR-1) negative log of the antagonist 0.000000003 9 0.3333 -0.48 8.52 0.000000005 12 0.2000 -0.70 8.30 0.000000010 24 0.1000 -1.00 8.00 0.000000030 40 0.0333 -1.48 7.52 0.000000050 46 0.0200 -1.70 7.30 0.000000100 50 0.0100 -2.00 7.00 0.000000300 54 0.0033 -2.48 6.52 0.000000500 54 0.0020 -2.70 6.30 0.000000125 Equipotent concentration ratio The negative log of the antagonist concentration (x-axis) against the log of the (ECR-1) The slope parameter is -1.064 and the intercept parameter is 9.438 which is pM2 value. The pM2 value is negative logarithm of the molar concentration of the antagonist which will reduce the effect of a multiple dose of the agonist (x) to that of a single dose The estimated regression equation for the data is Y = 9.438 – 1.064 X. The slope parameter is the average increment in the dependent variable when the dependent variable increases by one unit. The graph slopes from upper left of the scatter plot to lower right suggesting a negative relationship between the two variables. 1X10-8 Concentration-effect curves for histamine-induced effect of guinea-pig ileum in the presence and absence of concentration of mepyramine From the concentration-effect curves, the dose that is necessary to produce a response that is equal 50% of the maximum response induced values for mepyramine were determined to be 2.49x10-7. This means that the maximum response produced by histamine was depressed thus it means they were ineffective. It is important in order to reduce the negative effects caused by the histamine at these levels. This concentration is one of the most effective long-term measures of dosage usage. The ED50 values for mepyramine after histamine-induced effect of guinea-pig ileum of 1X10-8. Maximal contractions induced by the histamine-induced were using mean + standard error of the mean. At 1X10-8 the response produced histamine was not significant although there is inducement of short circuit current. The main response non effectiveness of mepyramine is because histamine was blocked. Histamine influences mepyramine exchange process thus acting as receptors as it produces a dose-related contraction with a similar potency. This supported by constant oscillation of the curve up and down as the concentration changes. Then calculate equipotent concentration ratios (ECR). Conc Histamine Mepyramine 1 x 10-8 M ECR the log of the (ECR-1) negative log of the antagonist 0.000000005 2 2.000 0.301 8.301 0.00000001 5 1.000 0.000 8.000 0.00000003 15 0.333 -0.477 7.523 0.00000005 22 0.200 -0.699 7.301 0.0000001 33 0.100 -1.000 7.000 0.0000003 43 0.033 -1.477 6.523 0.0000005 50 0.020 -1.699 6.301 0.000001 55 0.010 -2.000 6.000 the negative log of the antagonist concentration (x-axis) against the log of the (ECR-1). The slope parameter is -1.038 and the intercept parameter is 8.027 which is pM2 value. The pM2 value is negative logarithm of the molar concentration of the antagonist which will reduce the effect of a multiple dose of the agonist (x) to that of a single dose The estimated regression equation for the data is Y = 8.027 – 1.038 X. The slope parameter is the average increment in the dependent variable when the dependent variable increases by one unit. The graph slopes from upper left of the scatter plot to lower right suggesting a negative relationship between the two variables. 1X10-7 Concentration-effect curves for histamine-induced effect of guinea-pig ileum in the presence and absence of concentration of mepyramine From the concentration-effect curve above, the dose that is necessary to produce a response that is equal 50% of the maximum response induced values for Mepyramine were determined to be 6.2x10-6. This means that the maximum response produced by histamine was depressed thus it means they were ineffective. It is important in order to reduce the negative effects caused by the histamine at these levels. This concentration is one of the most effective long-term measures of dosage usage. The ED50 values for Mepyramine after histamine-induced effect of guinea-pig ileum of 1X10-7. At 1X10-7 the response produced histamine was not significant although there is inducement of short circuit current. The main response non effectiveness of Mepyramine is because histamine was blocked. Histamine influences Mepyramine exchange process thus acting as receptors as it produces a dose-related contraction with a similar potency. This supported by constant oscillation of the curve up and down as the concentration changes. Then calculate equipotent concentration ratios (ECR). Conc Histamine Mepyramine 1 x 10-7 M ecr the log of the (ECR-1) negative log of the antagonist 0.0000001 2 0.100 1.000 7.000 0.0000003 15 0.033 1.477 6.523 0.0000005 20 0.020 1.699 6.301 0.0000010 31 0.010 2.000 6.000 0.0000030 46 0.003 2.477 5.523 0.0000050 51 0.002 2.699 5.301 0.0000100 53 0.001 3.000 5.000 0.000030 55 0.000 3.477 4.523 the negative log of the antagonist concentration (x-axis) against the log of the (ECR-1). The slope parameter is -0.985 and the intercept parameter is 7.957 which is pM2 value. The pM2 value is negative logarithm of the molar concentration of the antagonist which will reduce the effect of a multiple dose of the agonist (x) to that of a single dose The estimated regression equation for the data is Y = 7.957 – 0.985 X. The slope parameter is the average increment in the dependent variable when the dependent variable increases by one unit. The graph slopes from upper left of the scatter plot to lower right suggesting a negative relationship between the two variables. Control Concentration-effect curves for histamine-induced effect of guinea-pig ileum in the presence and absence of the concentrations of mepyramine From the concentration-effect curve above, the dose that is necessary to produce a response that is equal 50% of the maximum response induced values for Mepyramine were determined to be 2.49x10-8. This means that the maximum response produced by histamine was depressed thus it means they were ineffective. It is important in order to reduce the negative effects caused by the histamine at these levels. This concentration is one of the most effective long-term measures of dosage usage. The ED50 values for Mepyramine after histamine-induced effect of guinea-pig ileum of control. The control the response produced histamine was not significant although there is inducement of short circuit current. The main response non effectiveness of Mepyramine is because histamine was blocked. Histamine influences Mepyramine exchange process thus acting as receptors as it produces a dose-related contraction with a similar potency. This supported by constant oscillation of the curve up and down as the concentration changes whose height increases as the number of responses increases. Then calculate equipotent concentration ratios (ECR). Conc Histamine control ECR the log of the (ECR-1) negative log of the antagonist 0.0000000005 1 20.000 1.301 9.301 0.000000001 6 10.000 1.000 9.000 0.000000003 14 3.333 0.523 8.523 0.000000005 25 2.000 0.301 8.301 0.00000001 32 1.000 0.000 8.000 0.00000003 47 0.333 -0.477 7.523 0.00000005 52 0.200 -0.699 7.301 0.0000001 52 0.100 -1.000 7.000 The negative log of the antagonist concentration (x-axis) against the log of the (ECR-1) The slope and pM2 values between Mepyramine without and in the presence of increasing concentrations of histamine was calculated using log (dose ratio -1) which was plotted against the negative logarithm of mol/l of histamine. The slope of this plot was -1.24 while pM2 value is represented by the point of intersection of the regression line and was found to be 9.7. The estimated regression equation for the data is Y = 9.7 – 1.24 X. The slope parameter is the average increment in the dependent variable when the dependent variable increases by one unit. The graph slopes from upper left of the scatter plot to lower right suggesting a negative relationship between the two variables. References Hishinuma S. & Young JM., 1995. Characteristics of the binding of [3H]- mepyramine to intact human U373 MG astrocytoma cells: evidence for histamine-induced H1-receptor internalisation. Br J Pharmacol. 1995;116:2715–2723. Hishinuma, S., Sato Y., Akatsu, C. & Masaru Shoji, M., 2012. The Affinity of Histamine for Gq Protein-Coupled Histamine H1-Receptors Is Predominantly Regulated by Their Internalization in Human Astrocytoma Cells. Journal of Pharmacological Sciences- The Japanese Pharmacological Society. Hishinuma S, Sato Y, Kobayashi Y, Komazaki H, & Saito M., 2008. Intact cell binding for in vitro prediction of sedative and non-sedative histamine H1-receptor antagonists based on receptor internalization. J Pharmacol Sci. 2008; 107:66–79. Linaker, B D , McKay, J S, Higgs, N B & Turnberg, L A., 1981. Mechanisms of histamine stimulated secretion in rabbit ileal mucosa. the Department of Medicine, Hope Hospital (University of Manchester School of Medicine), Salford, Lancashire. Nijkamp, F.P. & Van Ree, J.M., 1980. Effects of Endorphins On Different Parts Of The Gastrointestinal Tract Of Rat And Guinea-Pig In Vitro. Rudolph Magnus Institute for Pharmacology, University of Utrecht, Utrecht, the Netherlands Smit MJ, Timmerman H, Hijzelendoorn JC, Fukui H, Leurs R., 1996. Regulation of the human histamine H1 receptor stably expressed in Chinese hamster ovary cells. Br J Pharmacol. 1996;117:1071–1080. Martinez-Mir,I M.,Estan L., Morales-oliva, Rubio, E., 1992. Effect of histamine and histamine analogues on human isolated myometrial strips. Departament de Farmacologia, Universitat de Valencia, Valencia, Spain Read More