Catalytic receptors: They are membrane bound enzymes with a ligand binding site and a catalytic site whose activity is altered by the ligand. Examples are receptors for insulin, AT 2 angiotensin receptor, natriuretic peptide, prolactin, TLR and TNF. Insulin and prolactin receptors have tyrosine kinase activity.
Nuclear receptors: They are activated by lipid soluble agents that can easily cross the plasma membrane. They have a DNA binding domain that contains zinc finger motifs and a ligand binding domain at the carboxy terminal. The receptors can exist as monomers, homodimers or heterodimers and recognize DNA sequences termed hormone response elements. Once activated, they influence transcription by interactions with co-activators, co-repressors
Estrogen, testosterone, glucocorticoids, mineralocorticoids, progesterone, retinoic acid, PPAR gamma, thyroid hormone and Vitamin D3
G protein coupled receptors (GPCR) or metabotropic receptors: When a ligand binds to a GPCR a conformational change occurs, which then activates an associated G protein by exchanging its bound GDP for a GTP. The α subunit of the G protein, together with the bound GTP, then dissociates from the β and γ subunits. An intracellular signal cascade is activated that then activates or inhibits various target enzymes. Second messengers are produced which depend on the type of G protein activated.
| Gq | Gs | Gi/o |
| Alpha 1, angiotensin AT1, bradykinin, calcitonin, muscarinic, 5 HT, CCK, endothelin, glutamate, GnRH, histamine, motilin, oxytocin, PTH, vasopressin (V1) | Adenosine,beta receptors, calcitonin, CCK, CRH, dopamine, endothelin, estrogen, glucagon, PTH, vasopressin (V2) | 5 HT, muscarinic, adenosine, alpha 2, chemokines, dopamine, endothelin, GABA B, glutamate, histamine, melatonin, opioid, oxytocin, |
Dose response curves, efficacy and potency: The drug dose and response is plotted on a graph with the dose or log of dose on the X axis and the effect or response on the Y axis. The effect of a drug is related to the concentration of the drug at its site of action. Typically, the dose response curve is hyperbolic as the maximum effect of the drug is reached when all the receptors are occupied. When plotted on a graph with drug concentrations in logarithmic scale, the curve is sigmoid or S-shaped.
Potency is the amount of drug required to produce a desired effect. EC50 or ED50 can be used to evaluate or compare the potency of a drug (s). EC50 is the concentration of the drug that produces 50% of the maximum response. ED 50 is the same but stated as the drug dose (D). If two drugs have different potencies then , to get the same effect, we have to increase the dose of the less potent drug. A drug which is more potent can be said to have a higher affinity to the receptor and vice versa.
Efficacy is the maximum effect produced by a drug. It can be evaluated by the height of the dose-response curve. Full agonists will have more efficacy than partial agonists. Partial agonists bind to a receptor to produce less than maximal activation.
Drug-receptor interaction: Kd or equilibrium dissociation constant represents the concentration of ligand occupying half of the maximum receptor population. It is a measure of affinity. Emax is the maximum response while B max is the total number of receptors. A full response can be elicited by an agonist drug even if only 10% of the receptors are occupied. Antagonists can be either competitive (reversible) or non-competitive (irreversible).
Allosteric modulators: A drug that binds to a receptor at a site distinct from the active site and induces a conformational change in the receptor, which alters the affinity of the receptor for the endogenous ligand. Positive allosteric modulators increase the affinity, while negative allosteric modulators decrease the affinity. Examples are benzodiazepines and barbiturates on GABA A receptors.
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