Organ Bath Experimentation & Dose Response Curves

Question: Discuss about theOrgan Bath Experimentation Dose Response Curves. Answer: Introduction An example of an agonist that can cause contraction of smooth muscles is norepinephrine, while epinephrine antagonises the action. The agonist norepinephrine binds to specific receptors on the vascular smooth muscle hence leading to contraction of these muscles. The contraction action involves a number of signal transduction pathways which causes an increase in the intracellular calcium. Contraction of the vascular smooth muscle is stimulated by the intracellular calcium. Other typical agonists include angiotensin, vasopressin II, thromboxane A2 and endothelin-1 (Webb et al. 2003). Dose Response Curve Log-Dose Response Curve The difference between the two curves is that dose-response curve takes a rectangular hyperbole shape while the log-dose response curve takes a sigmoidal shape. The hyperbole in the dose-response curve is shed up and left, whereas using a logarithmic scale produces a semi-log curve that approaches the minimum value on the Y axis to the left and the maximum value to the right. The sigmoid curve is also exponential near these maximum and minimum values. When the dose indicated on the X-axis is based on an arithmetic scale produces a hyperbolic curve indicating a non-linear relationship. Whereas, presenting the dose on a log scale generates a sigmoid shaped curve (semi-log dose-response curve). Plotting the relation between the dosage on the X-axis against the drug response on the Y axis on a logarithmic scale produces a sigmoidal- shaped curve. Presenting the relation between the two variables in this manner is more useful compared to the linear plotting. This is attributed to the fact that a logarithmic presentation makes the dose scale in the region which rapid response changes to be more pronounced. Also, it compresses the scale on the side characterised by higher doses with significant changes which however produce an insignificant effect on the response (International Union of Basic and Clinical Pharmacology 2016). Log-dose response curve for the agonist, agonist + antagonist X, and agonist + antagonist Y Antagonist Y is the reversible competitive antagonist while antagonist X is the irreversible competitive antagonist. A reversible competitive antagonist causes the curve to shift to higher doses, indicated by the shift from the horizontal to the right on the dose axis. An irreversible antagonist, on the other hand, leads to a downward shift of the maximum. Simply put, the reversible competitive antagonist has notably increased the ED50, whereas the irreversible competitive antagonist des not unless spare receptors are available (Golan 2011). The presence of reversible competitive antagonists leads to a displacement of the agonist dose-response curve to the right parallel to it. This is attributed to the reversible binding of the competitive antagonist. The reversible binding ability enables competition for the same binding sites. Increasing the concentration of the agonist can overturn this effect. An increased concentration of the agonist will in turn cause a rightward parallel shift of the agonists dose-response curve. Agonists can still produce a maximal effect even in the presence of competitive reversible antagonists. The only difference is that higher concentrations of agonists are required to achieve the same level of effect (Clarkson 2016). On the other hand, irreversible competitive antagonists bind irreversibly to same receptor site as the agonist by forming covalent bonds, or they can also cause a reduction in the binding of the agonist by an allosterism mechanism, regardless of binding to a different site. Irreversible competitive antagonists primarily reduce the maximal effect of the agonist. This may be indicated by a reduction in the slope of the curve. Compared to reversible competitive antagonists, increasing the concentration of agonists does not reverse the action of this group. References Clarkson, C.W., 2016. Basic Principles of Pharmacology. , pp.120. Golan, D.E., 2011. Principles of pharmacology?: the pathophysiologic basis of drug therapy., Lippincott Williams Wilkins. International Union of Basic and Clinical Pharmacology, 2016. Pharmacodynamics. Pharmacology Education Project, p. 1-3. Available at: https://www.pharmacologyeducation.org/pharmacology/pharmacodynamics [Accessed October 28, 2016]. Webb, R.C. et al., 2003. Smooth Muscle Contraction and Relaxation. Advances in Physiology Education, 27(4), pp.201206.