Presentation is loading. Please wait.

Presentation is loading. Please wait.

Receptors Lesson 8. Ligands & Receptors n Ligand l neurotransmitters l drugs n Receptor proteins l ligand binds to multiple receptors l receptor subtypes.

Similar presentations


Presentation on theme: "Receptors Lesson 8. Ligands & Receptors n Ligand l neurotransmitters l drugs n Receptor proteins l ligand binds to multiple receptors l receptor subtypes."— Presentation transcript:

1 Receptors Lesson 8

2 Ligands & Receptors n Ligand l neurotransmitters l drugs n Receptor proteins l ligand binds to multiple receptors l receptor subtypes l specificity ~

3 Ligand-Receptors Binding n Binding site l specific point of ligand & receptor n Affinity l attraction l physical & electrical fit n NT or drug binds to receptor l  or  activity of neuron l excite or inhibit n Drugs mimic or block NT message ~

4 Lock & Key Model n Receptor changes shape n Excitation or Inhibition? l Determined by nature of receptor l receptor subtypes n NOT NT ~ n NT binds to receptor l NT = key l Receptor = lock

5 Receptor A NT n ligand binds to receptor l activation: EPSP or IPSP ~

6 Receptor B Receptor A n Same NT can bind to different -R l different part of NT ~ NT

7 Receptor B Receptor A n Same NT can bind to different -R l different part of NT ~ NT

8 Receptor B Receptor A NT Specificity of drugs Drug A Drug B

9 Structure-activity relationship n NT fits receptor site u key & lock n Change structure of drug... l change its affinity u increase or decrease l may bind to different receptor n Behavior mediated by synaptic activity l most drugs act at synapse ~

10 RECEPTOR DRUG n ligand binding n drug fx ~ Amphetamine NH 2

11 RECEPTOR DRUG n ligand binding n drug fx ~ Amphetamine NH 2

12 RECEPTOR DRUG n Stronger binding n greater fx ~ NH 2 MDA

13 RECEPTOR DRUG n Stronger binding n greater fx ~ MDMA NH

14 Drug Interaction Terms n Agonist (AG) mimics or  NT effects n Antagonist (ANT) blocks or  NT effects ~

15 Drug Interaction Terms n Direct agonist l activates receptor n direct antagonist l also binds to postsynaptic receptor l does not activate n Indirect (agonist/antagonist) l affects other parts of synaptic transmission model ~

16 Drug Interaction Terms n Competitive antagonist l competes for same receptor site l < affinity of NT n Noncompetitive l same binding site, >> affinity than NT l or different binding site on receptor ~

17 Drug Interaction Terms n Allosteric interactions l At different site, same receptor l noncompetitive antagonism l Potentiation (agonistic) n Partial agonist l activates -R, but weaker than NT n Inverse Agonist l activates receptor l opposite effect of NT ~

18 RECEPTOR NT Antagonists NT ANT

19 RECEPTOR NT Antagonists NT ANT

20 Receptor Types n Ionotropic receptors l NT directly controls channel l fast & transient action l Rapid desensitization u Tachyphylaxis n Metabotropic receptors l G protein-coupled receptors l requires energy: GTP l neuromodulation ~

21 Metabotropic receptors n G protein-gated Ion Channels l Receptor indirectly controls channel l relatively fast n 2d messenger systems l Effects relatively slow l long-lasting l Signal amplification ~

22 G protein-gated Ion Channels R G GDP

23 G protein-gated Ion Channels R G GTP Pore

24 2d Messenger Effects n Modulate phosphorylation l activation of processes l Protein Kinases   l Protein Phosphatases   n Modulate gene expression l transcriptional factors l DNA  RNA  Proteins l e.g., -R up- or down-regulation ~

25 n External signal l NT = 1st messenger n Membrane-associated components l Receptor l Transducer l Primary effector n Intracellular l 2d messenger l Secondary effector ~ 2d Messenger Systems

26 G protein: Protein Phosphorylation Receptor trans- ducer primary effector external signal: nt 2d messenger secondary effector Receptor trans- ducer primary effector external signal: nt 2d messenger secondary effector GSGS norepinephrine cAMP protein kinase A  adrenergic -R adenylyl cyclase

27 2d Messenger Systems n External signal n Receptor n Transducer n Primary effector n 2d messenger n Secondary effector ~ n Norepinephrine n Beta-adrenergic-R n G s –protein n Adenylyl cyclase n cAMP n Protein Kinase A

28 G protein: Protein Phosphorylation R G GTP ACAC GDP * PKA

29 G protein: Protein Phosphorylation R ACAC PKA G GTP ATP cAMP P Pore


Download ppt "Receptors Lesson 8. Ligands & Receptors n Ligand l neurotransmitters l drugs n Receptor proteins l ligand binds to multiple receptors l receptor subtypes."

Similar presentations


Ads by Google