Receptors Functions and Signal Transduction L1- L2
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1 Receptors Functions and Signal Transduction L1- L2 Faisal I. Mohammed, MD, PhD University of Jordan 1
2 Introduction to Physiology ( ) Summer 2012 Subject Lecture No. Lecturer Pages in the 11 th edition. textbook Pages in the 12 th edition textbook Receptors: types and adaptation - Membrane or intracellular - Ion channels - G-protein - Enzyme linked - Intracellular - Second messengers - camp and cgmp, Phospholipid - Calcium calmodulin and IRS Dr. Faisal Signal Transduction (Regulation of cellular machinery) Extracellular regulators: nervous, endocrine, paracrine and autocrine Steroids: Their Signal Transduction And Mechanism Of Action Dr. Faisal Dr. Faisal Microcirculation: Capillary Structure; Fluid Filtration (Forces) & Reabsorption - Starling Law Of Capillary Exchange - Lymphatic System Dr. Faisal Action Potential: Cardiac Action Potential (Fast Response AP) Vs Slow Response AP (The Pacemaker Concept) Dr. Faisal (FM) Textbook: Guyton Medical Textbook of Physiology By: Guyton and Hall 12 th edition
3 Objectives n Define first messenger (Hormones) n List hormone types n Describe receptor types n Outline the hormone receptors interactions n Describe second messenger mechanism of action n List second messengers University of Jordan 3
4 University of Jordan 4
5 University of Jordan 5
6 University of Jordan 6
7 Intercellular Communication Endocrine Cell Hormone Blood Target Cell Hormone Neuroendocrine Neuron Hormone Blood Target Cell Hormone Paracrine Cell Interstitial Fluid Target Cell Hormone Hormone Autocrine Cell Hormone Interstitial Fluid
8 University of Jordan 8
9 GAS MOLECULE University of Jordan 9
10 University of Jordan 10
11 University of Jordan 11
12 University of Jordan 12
13 Endocrine Glands and Hormones n Neurohormone: q Specialized neurons that secrete chemicals into the blood rather than synaptic cleft. n Chemical secreted is called neurohormone. n Hormones: q Affect metabolism of target organs. n Help regulate total body metabolism, growth, and reproduction. University of Jordan 13
14 Classes of Hormones Peptide & Protein Hormones Steroid Hormones Amine Hormones Gas Nitric Oxide (NO) University of Jordan 14
15 n Hormone types q Circulating circulate in blood throughout body q Local hormones act locally n Paracrine act on neighboring cells n Autocrine act on the same cell that secreted them University of Jordan 15
16 University of Jordan 16
17 Chemical classes of hormones q Lipid-soluble use transport proteins q Steroid: Lipids derived from cholesterol. q Are lipophilic hormones. q Testosterone. q Estradiol. q Cortisol. q Progesterone. q Thyroid q Nitric oxide (NO) University of Jordan 17
18 Chemical classes of hormones cont q Water-soluble circulate in free form q Amines: q Hormones derived from tyrosine and tryptophan. q Polypeptides and proteins: q Polypeptides: q Chains of < 100 amino acids in length. q ADH. q Protein hormones: q Polypeptide chains with > 100 amino acids. q Growth hormone. q Eicosanoid (prostaglandins) University of Jordan 18
19 Chemical Classification of Hormones cont n n Glycoproteins: q Long polypeptides (>100) bound to 1 or more carbohydrate (CHO) groups. n FSH and LH, TSH and hcg (human chorionic gonadotropin) They have α and β subunits (α is common and β is specific) Hormones can also be divided into: q Polar: n H 2 0 soluble. q Nonpolar (lipophilic): n H 2 0 insoluble. q Can gain entry into target cells. q Steroid hormones and T 4. University of Jordan 19
20 Prohormones and Prehormones n n n Prohormone: q Precursor is a longer chained polypeptide that is cut and spliced together to make the hormone. n Proinsulin. Preprohormone: q Prohormone derived from larger precursor molecule. n Preproinsulin. Prehormone: q Molecules secreted by endocrine glands that are inactive until changed into hormones by target cells. n T 4 converted to T 3. University of Jordan 20
21 Peptide & Protein Hormones Gland/Tissue Hormones Gland/Tissue Hormones Hypothalamus n TRH, GnRH, CRH GHRH, Somatostatin, Placenta n HCG, HCS or HPL Anterior pituitary n ACTH, TSH, FSH, LH, PRL, GH Kidney n Renin Posterior pituitary n Oxytocin, ADH Heart n ANP Thyroid n Calcitonin G.I. tract n Gastrin, CCK, Pancreas n Insulin,Glucagon, Somatostatin Secretin, GIP, Somatostatin Liver n Somatomedin C (IGF-1) Adipocyte n Leptin Parathyroid n PTH Adrenal medulla n Norepinephrine, epinephrine University of Jordan 21
22 Synthesis and secretion of peptide hormones University of Jordan 22
23 Amine Hormones Gland/Tissue Hypothalamus Hormones n Dopamine Thyroid n T 3, T 4 Adrenal medulla n NE, EPI University of Jordan 23
24 Synthesis of Amine Hormones tyrosine hydroxylase dopa decarboxylase L-Dopa Tyrosine Dopaminergic Neurons Dopamine dopamine β - hydroxylase Adrenergic Neurons phenylethanolamine- N-methyltransferase Norepinephrine Epinephrine Adrenal Glands Thyroid Hormones Thyroid Gland
25 Steroid Hormones Adrenal Cortex Testes Gland/Tissue Hormones n Cortisol, Aldosterone, Androgens n Testosterone Ovaries Corpus Luteum n Estrogens, Progesterone n Estrogens, Progesterone Placenta Kidney n Estrogens, Progesterone n 1,25-Dihydroxycholecalciferol (calcitriol) University of Jordan 25
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27 Hormone Activity n Hormones affect only specific target tissues with specific receptors n Receptors are dynamic and constantly synthesized and broken down q Down-regulation q Up-regulation University of Jordan 27
28 Effects of [Hormone] on Tissue Response n n Priming effect (upregulation): q Increase number of receptors formed on target cells in response to particular hormone. q Greater response by the target cell. Desensitization (downregulation): q Prolonged exposure to high [polypeptide hormone]. n Subsequent exposure to the same [hormone] produces less response. q Decrease in number of receptors on target cells. Insulin in adipose cells. q Pulsatile secretion may prevent downregulation. University of Jordan 28
29 Effects of [Hormone] on Tissue Response n [Hormone] in blood reflects the rate of secretion. n Half-life: q Time required for the blood [hormone] to be reduced to ½ reference level. n Minutes to days. n Normal tissue responses are produced only when [hormone] are present within physiological range. n Varying [hormone] within normal, physiological range can affect the responsiveness of target cells. University of Jordan 29
30 University of Jordan 30
31 University of Jordan 31
32 Mechanisms of Hormone Action n n Hormones of same chemical class have similar mechanisms of action. q Similarities include: n Location of cellular receptor proteins depends on the chemical nature of the hormone. n Events that occur in the target cells. To respond to a hormone: q Target cell must have specific receptors for that hormone (specificity). n Hormones exhibit: q Affinity (bind to receptors with high bond strength). q Saturation (low capacity of receptors). University of Jordan 32
33 Mechanisms of Hormone Action ± Response depends on both hormone and target cell ± Lipid-soluble hormones bind to receptors inside target cells ± Water-soluble hormones bind to receptors on the plasma membrane ± Activates second messenger system ± Amplification of original small signal ± Responsiveness of target cell depends on ± Hormone s concentration ± Abundance of target cell receptors University of Jordan 33
34 Receptor Receptors are specific membrane proteins, which are able to recognize and bind to corresponding ligand molecules, become activated, and transduce signal to next signaling molecules. Glycoprotein or Lipoprotein University of Jordan 34
35 ligand A small molecule that binds specifically to a larger one; for example, a hormone is the ligand for its specific protein receptor. University of Jordan 35
36 n Membrane receptors membrane Glycoprotein n Intracellular receptors Cytosol or nuclei DNA binding protein University of Jordan 36
37 1. membrane receptors (1) Ligand-gate ion channels type (cyclic receptor) ligand receptor ion channel open or close University of Jordan 37
38 University of Jordan 38
39 University of Jordan 39
40 University of Jordan 40
41 (2) G Protein-Coupled Receptors 1) 7-helices transmembrane receptor University of Jordan 41
42 Oligosaccharide unit Cytosolic side University of Jordan 42
43 2) G protein (Guanylate binding protein) n G protein refers to any protein which binds to GDP or GTP and act as signal transduction. n G proteins consist of three different subunits (α, β, γ- subunit) bound to GDP when exchanged to GTP activate α-subunit n α-subunit carries GTPase activity, binding and hydrolysis of GTP. University of Jordan 43
44 University of Jordan 44
45 University of Jordan 45
46 Neurotransmitter Second Messenger System University of Jordan 46
47 University of Jordan 47
48 camp ATP University of Jordan 48
49 - Pathway of G protein linked receptor H R G protein Es secondary messeger Protein kinase Phophorylation of Es or functional protein Biological effect University of Jordan 49
50 Properties of binding of H and R n highly specificity n highly affinity n saturation n reversible binding n special function model University of Jordan 50
51 Receptor Types n Channel-linked receptors q Ionotropic n Enzyme-linked receptors q Protein kinases à phosphorylation q Neurotrophins n G-protein-coupled receptors q Metabotropic n Intracellular receptors q Activation by cell-permeant signals ~ University of Jordan 51
52 University of Jordan 52
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