Receptors: Understanding Types and Functions

Receptors are specialized protein molecules found on the surface of cells or within cells. They bind to specific molecules such as hormones, neurotransmitters, or drugs, leading to a cellular response.

1. RECEPTORS It is defined as a macromolecule or binding site located on the surface or inside the effector cell that serves to recognize the signal molecule/drug and initiate the response to it, but itself has no other function. Two essential functions, viz, recognition of the specific ligand molecule and transduction of the signal into a response. Receptor molecule has a ligand binding domain and an effector domain (functional conformational change) Dr. BK Shoraisham JR Dept of Pharmacology

2. RECEPTORS TYPES OF RECEPTORS Ligand Gated ion Channel Receptor G Protein coupled receptors Intracellular receptors Enzyme linked receptors Transmembrane JAK-STAT binding receptors It is defined as a macromolecule or binding site located on the surface or inside the effector cell that serves to recognize the signal molecule/drug and initiate the response to it, but itself has no other function. Two essential functions, viz, recognition of the specific ligand molecule and transduction of the signal into a response. Receptor molecule has a ligand binding domain and an effector domain (functional conformational change)

3. TYPES OF RECEPTORS Ligand Gated ion Channel Receptor Enzyme linked receptors G Protein coupled receptors Intracellular receptors RECEPTORS Transmembrane JAK-STAT binding receptors

4. TYPES OF RECEPTORS Ligand Gated ion Channel Receptor G Protein coupled receptors Enzyme linked receptors Intracellular receptors EXAMPLES Transmembrane JAK-STAT binding receptors Nicotinic receptors 5-HT3 receptors GABAa receptors NMDA receptors

5. TYPES OF RECEPTORS Ligand Gated ion Channel Receptor G Protein coupled receptors Nicotinic receptors 5-HT3 receptors GABAa receptors NMDA receptors Enzyme linked receptors Intracellular receptors Muscarinic receptors Adrenoreceptors Histamine Receptors Serotonin receptors Opioids Receptors etc. EXAMPLES Transmembrane JAK-STAT binding receptors

6. TYPES OF RECEPTORS Ligand Gated ion Channel Receptor G Protein coupled receptors Enzyme linked receptors Intracellular receptors Nicotinic receptors 5-HT3 receptors GABAa receptors NMDA receptors EXAMPLES 5HT (Serotonin) 5HT3 (CTZ) Na+ Influx Vomiting Acetylcholine Nm (Skeletal Muscle) Na+ Influx Muscle Contraction Transmembrane JAK-STAT binding receptors

7. TYPES OF RECEPTORS Ligand Gated ion Channel Receptor G Protein coupled receptors Enzyme linked receptors Intracellular receptors Nicotinic receptors 5-HT3 receptors GABAa receptors NMDA receptors EXAMPLES 5HT (Serotonin) 5HT3 (CTZ) Na+ Influx Vomiting Acetylcholine Nm (Skeletal Muscle) Na+ Influx Muscle Contraction Transmembrane JAK-STAT binding receptors *GPCR superfamily-largest and most diverse group of proteins *seven-transmembrane , serpentine, G protein–linked receptors

8. TYPES OF RECEPTORS Ligand Gated ion Channel Receptor Examples G Protein coupled receptors Kinase linked receptors Intracellular receptors Nicotinic acetylcholine receptors GABAa Receptors Examples of GPCRs Muscarinic receptors [M1-M5] Adrenergic receptors [ α and β] Histamine receptors [H1-H3] Dopamine receptors [D1-D5] Opioid receptors [ μ κ б] 5- HT receptors 5-HT[1-7] except 5- HT3 GABAb receptors Adenyl cyclase- cAMP Phospholipase-C-inositol phosphate Ion Channels *GPCR superfamily-largest and most diverse group of proteins *seven-transmembrane , serpentine, G protein–linked receptors Transmembrane JAK-STAT binding receptors Gs : Adenylyl cyclase , Ca2+ channel Gi : Adenylyl cyclase, K+ channel opening Go : Ca2+ channel inhibition Gq : Phospholipase C

9. TYPES OF RECEPTORS Ligand Gated ion Channel Receptor Examples G Protein coupled receptors Kinase linked receptors Intracellular receptors Examples of GPCRs Muscarinic receptors [M1-M5] Adrenergic receptors [ α and β] Histamine receptors [H1-H3] Dopamine receptors [D1-D5] Opioid receptors [ μ κ б] 5- HT receptors 5-HT[1-7] except 5- HT3 GABAb receptors Transmembrane JAK-STAT binding receptors Adenyl cyclase- cAMP Phospholipase-C: IP3-DAG Ion Channels Gs : Adenylyl cyclase , Ca2+ channel Gi : Adenylyl cyclase, K+ channel opening Go : Ca2+ channel inhibition Gq : Phospholipase C

10. TYPES OF RECEPTORS Ligand Gated ion Channel Receptor Examples G Protein coupled receptors Kinase linked receptors Intracellular receptors Muscarinic receptors Adrenoreceptors Histamine Receptors Serotonin receptors Opioids Receptors etc. Adenyl cyclase- cAMP Phospholipase-C: IP3-DAG Ion Channels Three effector systems Transmembrane JAK-STAT binding receptors

11. G Protein coupled receptors Adenyl cyclase- cAMP Ion Channels Phospholipase-C: IP3-DAG

12. G Protein coupled receptors Effects of cAMP on Organs Ion Channels Phospholipase-C: IP3-DAG PKA phosphorylates many functional proteins including troponin and phospholamban, they interact with Ca2+ and also Calcium is made available by entry from outside (direct activation of myocardial membrane Ca2+ channels by Gsα and through their phosphorylation by PKA) as well as from intracellular stores. Increases force of contraction, Increase Heart rate, Increases Blood pressure.

13. G Protein coupled receptors Effects of cAMP on Organs Ion Channels Phospholipase-C: IP3-DAG PKA then phosphorylates a number of enzymes involved in lipolysis, including hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL). HSL and ATGL are responsible for hydrolyzing triglycerides into free fatty acids and glycerol causing Lipolysis

14. G Protein coupled receptors Effects of cAMP on Organs Ion Channels Phospholipase-C: IP3-DAG The effects of cAMP on liver glycogenolysis Activates glycogen phosphorylase Inhibits glycogen synthase:  cAMP inhibits glycogen synthase Increases glucose production

15. G Protein coupled receptors Effects of cAMP on Organs Ion Channels Phospholipase-C: IP3-DAG cAMP has a relaxing effect on smooth muscle -Increasing the activity of the calcium pump removing calcium from the cytoplasm -Activating MLCP, which dephosphorylates MLCK. MLCK is an enzyme that phosphorylates myosin light chain, which is required for smooth muscle contraction -Inhibiting the release of calcium from the SR -Opening potassium channels, causing hyperpolarization and relaxation 

16. Adenyl cyclase- cAMP Phospholipase-C: IP3-DAG Ion Channels G Protein coupled receptors -The PLC, IP3, and DAG pathway is involved in the release of neurotransmitters from presynaptic terminals. -DAG can activate PKC, which can then phosphorylate and activate presynaptic proteins that are involved in vesicle release. CNS Stimulation

17. G Protein coupled receptors Adenyl cyclase- cAMP Phospholipase-C: IP3-DAG Effects on Organs Ion Channels -The PLC, IP3, and DAG pathway is involved in the release of neurotransmitters from presynaptic terminals. -DAG can activate PKC, which can then phosphorylate and activate presynaptic proteins that are involved in vesicle release. CNS Stimulation

18. G Protein coupled receptors Adenyl cyclase- cAMP Phospholipase-C: IP3-DAG Effects on Organs Ion Channels Smooth muscle contraction Vasoconstriction Bronchoconstriction Increased gastrointestinal motility Increased bladder contraction Mydriasis

19. G Protein coupled receptors Adenyl cyclase- cAMP Phospholipase-C: IP3-DAG Effects on Organs Ion Channels Increases force of contraction Increase Heart rate Increases Blood pressure

20. G Protein coupled receptors Adenyl cyclase- cAMP Phospholipase-C: IP3-DAG Effects on Organs Ion Channels I n the pituitary gland, the PLC/IP3/DAG pathway is activation leads to the release of growth hormone and thyrotropin, respectively. In the pancreas, the PLC/IP3/DAG pathway is activated by cholecystokinin (CCK). This leads to the release of insulin.

21. G Protein coupled receptors Adenyl cyclase- cAMP Phospholipase-C-inositol phosphate Ion Channels

22. G Protein coupled receptors Adenyl cyclase- cAMP Phospholipase-C-inositol phosphate Ion Channels Regulation K+ opening Adrenergic- α2 Muscarinic-M2 Dopamine-D2 5-HT1A GABAB Opioid-µ, δ Adenosine-A Ca2+ closing Dopamine-D2 GABAB Opioid- κ Adenosine-A1 Somatostatin Ca2+ opening Adrenergic- β1 large extracellular ligand binding domain connected through a single transmembrane helical peptide chain to an intracellular subunit having enzymatic property

23. G Protein coupled receptors Adenyl cyclase- cAMP Phospholipase-C-inositol phosphate Ion Channels Regulation K+ opening Adrenergic- α2 Muscarinic-M2 Dopamine-D2 5-HT1A GABAB Opioid-µ, δ Adenosine-A Ca2+ closing Dopamine-D2 GABAB Opioid- κ Adenosine-A1 Somatostatin Ca2+ opening Adrenergic- β1 large extracellular ligand binding domain connected through a single transmembrane helical peptide chain to an intracellular subunit having enzymatic property

24. G Protein coupled receptors Adenyl cyclase- cAMP Phospholipase-C-inositol phosphate Ion Channels Regulation K+ opening Adrenergic- α2 Muscarinic-M2 Dopamine-D2 5-HT1A GABAB Opioid-µ, δ Adenosine-A Ca2+ closing Dopamine-D2 GABAB Opioid- κ Adenosine-A1 Somatostatin Ca2+ opening Adrenergic- β1 large extracellular ligand binding domain connected through a single transmembrane helical peptide chain to an intracellular subunit having enzymatic property

25. TYPES OF RECEPTORS Ligand Gated ion Channel Receptor Examples G Protein coupled receptors Enzyme linked receptors Intracellular receptors large extracellular ligand binding domain connected through a single transmembrane helical peptide chain to an intracellular subunit having enzymatic property Utilized primarily by peptide hormones Receptor tyrosine kinases (RTKs) are the largest family of enzyme-linked receptors --Insulin receptor, Epidermal growth factor receptor (EGFR), Fibroblast growth factor receptor (FGFR), Platelet-derived growth factor receptor (PDGFR) Serine/threonine-specific protein kinases-- TGF- β receptor Guanylate cyclases --Atrial natriuretic peptide receptor (ANPR) --Brain natriuretic peptide receptor (BNPR) Transmembrane JAK-STAT binding receptors

26. TYPES OF RECEPTORS Ligand Gated ion Channel Receptor Examples G Protein coupled receptors Enzyme linked receptors Intracellular receptors Utilized primarily by peptide hormones Receptor tyrosine kinases (RTKs) are the largest family of enzyme-linked receptors --Insulin receptor, Epidermal growth factor receptor (EGFR), Fibroblast growth factor receptor (FGFR), Platelet-derived growth factor receptor (PDGFR) Serine/threonine-specific protein kinases- - TGF- β receptor Guanylate cyclases --Atrial natriuretic peptide receptor (ANPR) --Brain natriuretic peptide receptor (BNPR) EXAMPLES Transmembrane JAK-STAT binding receptors

27. TYPES OF RECEPTORS Ligand Gated ion Channel Receptor Examples G Protein coupled receptors Kinase linked receptors Intracellular receptors All steroidal hormones (glucocorticoids, mineralocorticoids, androgens, estrogens, progesterone) Thyroxine vit D and vit A Receptors Transmembrane JAK-STAT binding receptors

28. TYPES OF RECEPTORS Ligand Gated ion Channel Receptor Examples G Protein coupled receptors Kinase linked receptors Intracellular receptors All steroidal hormones (glucocorticoids, mineralocorticoids, androgens, estrogens, progesterone) Thyroxine vit D and vit A Receptors Transmembrane JAK-STAT binding receptors

29. TYPES OF RECEPTORS Ligand Gated ion Channel Receptor Examples G Protein coupled receptors Kinase linked receptors Intracellular receptors All steroidal hormones (glucocorticoids, mineralocorticoids, androgens, estrogens, progesterone) Thyroxine vit D and vit A Receptors Transmembrane JAK-STAT binding receptors Agonist-induced dimerization cytosolic tyrosine protein kinase JAK binds on intracellular domain JAK gets activated and phosphorylates tyrosine residues of the receptor ------------ free moving protein STAT binds to the receptor which is also phosphorylated by JAK --------------- Pairs of phosphorylated STAT dimerize and translocate to the nucleus to regulate gene transcription resulting in a biological response Many cytokines growth hormone Prolactin interferons, etc. act through this type of receptor

30. TYPES OF RECEPTORS Ligand Gated ion Channel Receptor Examples G Protein coupled receptors Kinase linked receptors Intracellular receptors All steroidal hormones (glucocorticoids, mineralocorticoids, androgens, estrogens, progesterone) Thyroxine vit D and vit A Receptors Transmembrane JAK-STAT binding receptors Many cytokines growth hormone Prolactin interferons, etc. act through this type of receptor