The Development of Receptor Theory Paul Erhlich(1854-1915)was a German bacteriologist who attempted to find a 'magic bullet'to cure syphilis and was a pioneer in the study of immunology.One of his findings was made when he incubated toxins with anti-toxins in a test tube.Erhlich found that antigen- antibody interactions are direct chemical encounters and not generalized phenomena as they require an ongoing biological process in the whole body.He also coined the term "chemotherapeutic index",meaning the ratio of the minimal curative dose to the maximal tolerated dose
The Development of Receptor Theory Paul Erhlich (1854-1915) was a German bacteriologist who attempted to find a 'magic bullet' to cure syphilis and was a pioneer in the study of immunology. One of his findings was made when he incubated toxins with anti-toxins in a test tube. Erhlich found that antigenantibody interactions are direct chemical encounters and not generalized phenomena as they require an ongoing biological process in the whole body. He also coined the term “chemotherapeutic index”, meaning the ratio of the minimal curative dose to the maximal tolerated dose
The Development of Receptor Theory John Newport Langley(1852-1926),a British physiologist, first coined the term "receptive substance".His work described curare as a blocker of neuromuscular transmission,as he was able to show that curare also could block chemical stimulation of frog gastrocnemius muscle by nicotine,without motor nerves.Therefore, there is a mutual antagonism between nicotine and curare,and the effect of which depends on the relative concentration of each.He also worked on atropine and pilocarpine,and the work led to the hypothesis that both atropine and pilocarpine could form a complex with a common substance at the nerve end,which we now know are the muscarinic receptors
The Development of Receptor Theory John Newport Langley (1852-1926), a British physiologist, first coined the term “receptive substance”. His work described curare as a blocker of neuromuscular transmission, as he was able to show that curare also could block chemical stimulation of frog gastrocnemius muscle by nicotine, without motor nerves. Therefore, there is a mutual antagonism between nicotine and curare, and the effect of which depends on the relative concentration of each. He also worked on atropine and pilocarpine, and the work led to the hypothesis that both atropine and pilocarpine could form a complex with a common substance at the nerve end, which we now know are the muscarinic receptors
The Development of Receptor Theory Langley's work also led to the concept that the rate of combination(binding)and the saturable effects are characteristic of drug and receptor interactions.This concept was not readily accepted at that time.For instance,Henry H.Dale(1875-1968)thought that the differential effectiveness of adrenaline analogues in mimicking sympathetic functions in varying tissues does not necessarily imply the existence of specific chemical receptors on target tissues.Eventually, experimental data prove the presence of specific receptors for these (as we know today) pharmacological interactions
The Development of Receptor Theory Langley’s work also led to the concept that the rate of combination (binding) and the saturable effects are characteristic of drug and receptor interactions. This concept was not readily accepted at that time. For instance, Henry H. Dale (1875-1968) thought that the differential effectiveness of adrenaline analogues in mimicking sympathetic functions in varying tissues does not necessarily imply the existence of specific chemical receptors on target tissues. Eventually, experimental data prove the presence of specific receptors for these (as we know today) pharmacological interactions
Receptors as Enzymes: nicotinic acetylcholine R G Protein-Coupled Receptor Systems glutamate R binding GABAA R glycine R 5HTa serotonin R G protein- coupled receptors Cell Surface Multisubunit Ligand-gated lon channels GTP GDP catalysis Catalytic Activities: G Proteins: Effectors Tyrosine kinases growth factor receptors Defined by Regulated by Cytoplasm neurotrophic factor receptors a Subunit a Subunits: Tyrosine phosphatases composition Serine/threonine kinases Cs ↑adenylyl cyclase,↑Ca2+currents TGFB-receptor % adenylyl cyclase,K+currents Guanylyl cyclase 00 Ca2+currents ANF receptor da ↑phospholipase CB guanylin receptor 13 Na+/H+exchange 0 1 cGMP-phosphodiesterase(vision) Cytosolic Colit t adenylyl cyclase(olfaction) Nucleus Receptor regulated by Regulation of transcription By subunits: steroids retinoids receptor-operated K+currents thyroid hormone adenylyl cyclase phospholipase CB Figure 2-1.Structural motifs of physiological receptors and their relationships to signaling pathways