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Hormones, Receptors, and Communication Between Cells

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Presentation on theme: "Hormones, Receptors, and Communication Between Cells"— Presentation transcript:

1 Hormones, Receptors, and Communication Between Cells

2 General principles

3 Selected hormones & their functions
Insulin Pancreas Controls blood-sugar level and storage of glycogen. Glucagon Pancreas Stimulates conversion of glycogen to glucose; raises blood sugar level. Oxytocin Pituitary gland Stimulates contraction of the uterine muscles and secretion of milk by the mammary glands. Vasopressin Pituitary gland Controls water excretion by the kidneys; stimulates contraction of the blood vessels. Growth hormone Pituitary gland Stimulates growth. Adrenocorticotrophic Pituitary gland Stimulates the adrenal cortex, which,in turn,releases hormone (ACTH) several steroid hormones. Prolactin Pituitary gland Stimulates milk production by the mammary glands after birth of baby. Epinephrine Adrenal glands Stimulates rise in blood pressure, acceleration of heartbeat, decreased secretion of insulin, and increased blood sugar.

4 Hormones, Receptors, and Communication Between Cells
Intracellular receptors lipid soluble hormones Steroid hormones, vitamin D, retinoids, thyroxine Bind to intracellular protein receptors This binds to regulatory elements by a gene Alters the rate of gene transcription Induces or represses gene transcription

5 Hormones, Receptors, and Communication Between Cells
Intracellular Receptors

6 Hormones, Receptors, and Communication Between Cells
Cell-surface receptors Water soluble hormones Peptide hormones (insulin), catecholamines, neurotransmitters Three class of cell-surface receptors Ligand-Gated Receptors Catalytic Receptors G Protein-linked Receptors

7 Ligand-gated receptors
Binding of a ligand (often a neurotransmitter) affects flow of ions in/out of cell Gamma-amino butyric acid (GABA) binds and opens chloride channels in the brain Valium (anti-anxiety drug) reduces the amount of GABA required to open the chloride channels

8 Gated Channels Voltage Gated Ligand Gated

9 Catalytic receptors Binding of hormone activates tyrosine kinase on receptor which phosphorylates certain cellular proteins Insulin receptor is a catalytic receptor with TYR Kinase activity

10 Insulin Signal Transduction Cascades
Insulin Promotes Cell growth, Glucose uptake and storage Insulin Receptors (IR) bind 2 insulin peptide with 2 α chains β chains (auto-)phosphorylate each other P- β subunits now active tyrosine kinases Active RTK initiates a signal transduction cascade RTK phosphorylates Insulin Receptor Substrate-1 (IRS-1) Adaptor proteins Grb2 and Sos bind to P-Tyr- IRS-1 via SH2 domain Sos activates Ras GTPase Ras.GTP activatesProtein Kinase Cascade

11 Many enzymes are regulated by covalent attachment of phosphate, in ester linkage, to the side-chain hydroxyl group of a particular amino acid residue (serine, threonine, or tyrosine).

12 A protein kinase transfers the terminal phosphate of ATP to a hydroxyl group on a protein.
A protein phosphatase catalyzes removal of the Pi by hydrolysis.

13 Protein kinases and phosphatases are themselves regulated by complex signal cascades. For example:
Some protein kinases are activated by Ca++-calmodulin. Protein Kinase A is activated by cyclic-AMP (cAMP).

14 G-protein-linked receptors
Binding of hormone activates an enzyme via a G-protein communication link. The enzymes produces intracellular messengers cAMP diacylglycerol (DAG))

15 Intracellular Messengers: Signal Transduction Pathways
Cyclic AMP (cAMP) Diacylglycerol (DAG) & Inositol Triphosphate (IP3) Cyclic GMP (cGMP)

16 G-Protein-Linked Receptors:
Two types of G-Proteins Stimulating G protein (Gs) Activate adenylate cyclase Inhibitory G proteins (Gi) Inhibit adenylate cyclase

17 G Proteins G proteins are trimers Three protein units Alpha Beta gamma

18 Alpha proteins are different in Gs and Gi
Both have GTPase activity Alpha proteins modify adenylate cyclase activity AC stimulated by Alpha(s) when activated by a hormone AC Inhibited by Alpha(I) when activated by other hormones

19 The a subunit of a G-protein (Ga) binds GTP, & can hydrolyze it to GDP + Pi.
a & g subunits have covalently attached lipid anchors that bind a G-protein to the plasma membrane cytosolic surface. Adenylate Cyclase (AC) is a transmembrane protein, with cytosolic domains forming the catalytic site.

20 Family of G Proteins Binding of hormones to receptors causes:
GTP to displace GDP Dissociation of alpha protein from beta and gamma subunits activation of the alpha protein Inhibition or activation of adenylate cyclase GTPase gradually degrades GTP and inactivates the alpha protein effect (clock)

21 The cAMP Signal Transduction Pathway
cAMP – intracellular messenger Elevated cAMP can either activate or inhibit regulatory enzymes cAMP activates glycogen degradation cAMP inhibits glycogen synthesis [cAMP] affected by rates of synthesis and degradation Synthesis by adenylate cyclase Degradation by phosphodiesterase Stimulated by insulin Inhibited by caffeine

22 Activation of Protein Kinase A by cAMP
Activates or inhibits several enzymes of CHO and Lipid metabolism Inactive form: regulatory+catalytic subunits associated Active form: binding of cAMP disassociates subunits

23 Turn off of the signal: 1. Ga hydrolyzes GTP to GDP + Pi. (GTPase).
The presence of GDP on Ga causes it to rebind to the inhibitory bg complex. Adenylate Cyclase is no longer activated. 2. Phosphodiesterases catalyze hydrolysis of cAMP  AMP.

24 DAG & IP3 Phosphotidylinositol Signal Transduction Pathway
Protein kinase C activated by DAG and calcium Synthesis of DAG and IP3

25 cGMP The cGMP Signal Transduction Pathway
cGMP effects: lowering of blood pressure & decreasing CHD risk Relaxation of cardiac muscle Vasodilation of vascular smooth muscle Increased excretion of sodium and water by kidney Decreased aggregation by platelet cells

26 cGMP The cGMP Signal Transduction Pathway
Two forms of guanylate cyclase Membrane-bound Activated by ANF (atrial natriuretic factor) ANF released when BP elevated Cytosolic Activated by nitric oxide NO produced from arginine by NO synthase Nitroglycerine slowly produces NO, relaxes cardiac and vascular smooth muscle, reduces angina cAMP activates Protein Kinase G Phosphorylates smooth muscle proteins

27 cGMP The cGMP Signal Transduction Pathway

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