Human Physiology: Unit-1

Source: Collected from different sources on the internet and modified by Dr Boominathan Ph.D.

BYBYDR BOOMINATHAN Ph.D. DR BOOMINATHAN Ph.D.

M.Sc.,(Med. Bio, JIPMER), M.Sc.,(FGSWI, Israel), Ph.D (NUS, SINGAPORE)M.Sc.,(Med. Bio, JIPMER), M.Sc.,(FGSWI, Israel), Ph.D (NUS, SINGAPORE)

PONDICHERRY UNIVERSITYPONDICHERRY UNIVERSITYV LectureV Lecture

14/August/201214/August/2012

Intercellular Communication

Intercellular Commication

Intercellular Communication• Cells of body must communicate with one another• Coordinates organ systems• Takes place directly:

– Physical contact between cells• Gap junctions

• Direct linkage of surface markers

• Or indirectly – Extracellular chemical messengers or

signal molecules– Specific to target cell receptors

Chemical Messengers

• Four types of chemical messengers– Paracrines

• Local chemical messengers

• Exert effect only on neighboring cells in immediate environment of secretion site

– Neurotransmitters• Short-range chemical messengers

• Diffuse across narrow space to act locally on adjoining target cell (another neuron, a muscle, or a gland)

Extracellular signalingmolecules released by cells occurs over distancesfrom a few microns – autocrine (c)and paracrine (b) signaling toseveral meters in endocrine (a)signaling.

In some instances,receptor proteins attached to themembrane of one cell interactdirectly with receptors on anadjacent cell (d).

© 2000 by W. H. Freeman and Company. All rights reserved.

General Schemes of Intercellular Signalling

Paracrine secretion

Neurotransmitter secretion

Chemical Messengers

– Hormones• Long-range messengers• Secreted into blood by endocrine glands in response

to appropriate signal• Exert effect on target cells some distance away from

release site

– Neurohormones• Hormones released into blood by neurosecretory

neurons• Distributed through blood to distant target cells

Chemical Messengers• Cell responses brought about primarily by signal

transduction– Incoming signals conveyed to target cell’s interior

• Binding of extracellular messenger (first messenger) to receptor brings about intracellular response by either– Opening or closing channels

• Chemically gated receptor channel

– Activating second-messenger systems• Activated by first messenger

– Receptor-enzyme

• Relays message to intracellular proteins that carry out dictated response– G-protein coupled receptor

Receptor-enzyme:

Tyrosine kinase pathway

Hormones• Endocrinology

– Study of homeostatic activities accomplished by hormones

• Two distinct groups of hormones based on their solubility properties– Hydrophilic hormones

• Highly water soluble • Low lipid solubility

– Lipophilic hormones• High lipid solubility• Poorly soluble in water

Mechanism of hydrophilic hormones via cyclic AMP second messenger pathway

Mechanism of action of hormones

Lipophilic hormones

Hydrophilic hormones

Comparison of Nervous System and Endocrine System

Animation: Mechanism of action of a peptide hormone

Animation: Mechanism of action of a steroid hormone

Questions1. There are 3 ways cells communicate. The 2 direct means of

communication is through ___________ and _______________. Cells indirectly communicate through _______________.

2. Name and describe the 4 types of chemical messengers. Include which fluid medium they travel through: blood, extracellular fluid, intracellular fluid.

3. Why is a neurotransmitter different than paracrine signalling?

4. What is a ligand? What is a receptor?

5. How does a chemical messenger “know” which organ to affect?

6. Name 3 ways that an extracellular chemical messenger can bring about an intracellular response.

7. Is the response between a chemical messenger and a particular receptor always the same?

8. How can a chemical receptor elicit a different response inside a cell?

9. In a second messenger system, where does the first messenger bind? Where is the second messenger?

Questions11. There are 2 major 2nd messengers: cyclic AMP and Ca2+ . Describe the

action of a hydrophilic hormone via activation of the cyclic AMP 2nd messenger pathway. If you draw pictures, you must label everything and explain what is happening.

12. How does using an 2nd messenger system amplify the response inside the cell?

13. How do some chemical messengers affect gene activity (hence, protein synthesis) within a cell?

14. Which type of hormone can affect gene activity, hydrophilic or lipophilic? Why?

INTRACELLULAR SIGNAL TRANSDUCTION:A Journey from the Plasma Membrane to the Nucleus

(with interesting stops along the way)

Thanks toPaula Tracy, Ph.D.paula.tracy@uvm.edu

INTRACELLULAR SIGNALING:Signal Transduction

Cell membranes, as well as the cell cytoplasm and even the cell nucleus, contain cell-specific receptors for various ligands, which are involved in outside-inside signaling, i.e. signal transduction.

Ligands include hormones, growth factors, cytokines, prostaglandins and proteases.

Hormones are involved in a variety of metabolic processes that maintain homeostasise.g. fuel metabolism. Particularly noteworthy in that regard are glucagon, insulin ,epinephrine and norepinephrine.

Growth factors are involved in mitogenesis, whereas cytokines play critical roles in thedifferentiation, proliferation and function of various cell lineages..

Interaction of such ligands with their membrane, cell-specific receptors or intracellularreceptors causes conformational changes in the receptor and, in many instances receptor-associated cytoplasmic proteins.

Such events result in the initiation of a cascade of importance, but as yet incompletely understood, events leading to e.g. enzyme activation, differentiation and/or cell division.

Extracellular signalingmolecules released by cells occurs over distancesfrom a few microns – autocrine (c)and paracrine (b) signaling toseveral meters in endocrine (a)signaling.

In some instances,receptor proteins attached to themembrane of one cell interactdirectly with receptors on anadjacent cell (d).

© 2000 by W. H. Freeman and Company. All rights reserved.

General Schemes of Intercellular Signalling

FORCES DRIVING SELECTION OF CURRENT MECHANISMS

Need for coordinated intercellular communication

Need to translate extracellular signals into series of intracellular events, while allowing for specificity

Specificity Determinants: 1. Specific receptors on or in the target cells recognize an appropriate ligand. 2. Specific response to receptor occupancy - effector pathways

Diversity of intercellular communication is achieved with hundreds of signaling molecules, including...

Proteins, small peptides, amino acids, nucleotides, steroids, fatty acid derivatives, and even dissolved gases such as NO and CO

Intracellular receptors:- signaling molecules include steroid hormones, retinoids, thyroxine, etc- receptor-hormone complex acts a transcription factor to alter transcription of certain genes

Cell surface receptors:- signaling molecules include peptide hormones, ephineprines, insulin, growth factors, cytokines, etc-binding, and subsequent events, triggers an or in the cytosolic concentration of a second messenger; or the activated,bound receptor acts as a scaffold to recruit and activate other intracellular proteins

© 2000 by W. H. Freeman and Company. All rights reserved.

Receptor Classes

ADVANTAGES1. Each cell is programmed to respond to specific combinations of signaling molecules.2. Different cells can respond differently to the same chemical signal.

Molecular Biology of the Cell, 2002

HORMONES - First class of signaling molecules defined

Secreted from endocrine cells - specialized signaling cells that control the behavior of an organism as a whole:

1. Differ from other intracellular mediators2. Usually stimulate metabolic activities in tissues remote from the secretory organ3. Active at very low concentrations (pM - M)4. Response to hormonal signal comes as a direct and rapid result of its secretion5. Metabolized rapidly so effects are, in most instances, short-lived, leading to rapid adaptations to metabolic changes

1. Peptides or polypeptides - insulin, glucagon, growth hormone, insulin-like growth factors, vasopressin, prolactin….2. Glycoproteins - follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH)…3. Steroids - glucocorticoids (aldosterone, cortisol), steroids (progesterone, testosterone), retinoic acid…4. Amino acid derivatives - epinephrine, norepinephrine, thyroxine, triidothyronine

Hormone types:

AGONISTS vs. ANTAGONISTS

Agonist mimics a hormone in binding productively to a receptor

Antagonist mimics a hormone stereochemically, but binds to the receptornon-productively, inhibiting the action of the natural hormone

Hormonebinds 2 receptor in lung

bronchial relaxation

Agoniste.g. important therapy

in asthma

Antagonistcontrol heart beat

binds 2 receptor in heart muscle increased heart rate

RECEPTOR CHARACTERISTICS

1. Participates in transduction of the signal from the external messenger to some component of the metabolic machinery

2. Has at least one additional functional site which is altered by ligand binding (allosteric site)

3. Ligand binding to receptors is saturable, resembling Michaelis-Menten kinetics

4. Ligand-receptor interaction characterized by tight binding (Kd = pM - M)

© 2000 by W. H. Freeman and Company. All rights reserved.

Molecular Biology of the Cell, 2002

Simple Intracellular Signaling Induced by an Extracellular Signaling Molecule

A signaling molecule activates its receptor activation of an intracellular signaling pathway, i.e. a series of signalingproteins, which may interact with a target protein to change the behavior of the cell.

THREE LARGEST CLASSES OF CELL SURFACE RECEPTORS

GlucagonEpinephrineThrombin

InsulinGrowth factors

Molecular Biology of the Cell, 2002