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CPB11 and CPB12 Ligand Receptor Interactions I/II Define the terms 'ligands' and 'receptors'

Ligand A chemical which specifically binds to a receptor Agonist - Binds to a receptor and generates a receptor and causes a biological response Antagonist - Binds to a receptor and generates no response

Receptor A membrane protein which binds a drug Activation causes intracellular changes Drugs bind to specific receptors and saturate the binding We have receptors for hormones produced in the body (Ex: morphine receptors are present in the body because of endorphin hormone receptors) Possess structural and steric specificity Expressed in select tissues Saturable and finite (Limited number of binding sites) High affinity for the ligand o Ex: Adrenaline acts on the B1-adrenorecptor in the heart to increase the rate and force of cardiac contraction o Ex: Dopamine binds to dopamine receptors in the brain as a reward signal o Ex: Angiotensin will only act on angiotensin receptors on vascular NOT smooth tissue. Only on kidney epithelium but NOT intestinal epithelium. Tissue responses are generally directly proportional to the fraction of the receptors occupied with agonist Dose-response curve - Graph reaches a plateau where no more additional agonist has an effect on the response (No more receptors to bind to) EC50 = The 50% response of effective concentration between the baseline and max response (Compare drugs by looking at the dose that creates a 50% response)

Describe the way in which receptors are defined


Explain the concept of a dose-response relationships


(dose)-response curve is hyperbolic

Log(dose) response is sigmoid (Scurve)

Explain quantitative concepts [KD; Bmax; IC50/EC50 ]

KD must = [D] for 1/2 or 50%

Define 'agonists'; 'partial agonists'; 'intrinsic activity'


Agonist - Binds to a receptor and generates a receptor and causes a max response. Antagonist - Binds to a receptor and generates no response Partial agonist - An agonist which never produces a maximum response Intrinsic activity () - Ability to produce a response called Efficacy = 1: Full agonist 1>>0: Partial agonist = 0: Antagonist Spare receptors - some tissue has more receptors than is required for a full response Same drug, same system, far more receptors than tissue Low dose agonist = very effective, high dose of antagonist is necessary to block the response.

Explain the difference between reversible, irreversible, competitive, noncompetitive antagonists


Competitive antagonist - Binds to the same site as the agonist and two compete with each other. Shift of the dose-response curve to the right. Emax doesnt change, just need more drug to get it. Non-competitive antagonist - Antagonist binds to a different site to the agonist. It binds to a different site, adding more agonist will not make a different but the agonist can not attach because the pocket becomes closed. Curve doesnt shift to the right but Emax decreases. Irreversible antagonist - Bind to the drugs irreversibly. Binds there forever until receptor is degraded/destroyed.

Describe how each type of antagonist affects the dose-response curve


Competitive - Shift curve to the right, Emax does not change

Non-competitive - No shift in curve, but Emax decreases