Communication, Hardi

HOMEOSTASIS

COMMUNICATION Dr. Hardi Darmawan,MPH&TM.,FRSTM FK UNSRI

DEFINITION OF PHYSIOLOGY • Physiology is the study of how things work

BASIC PRINCIPLE OF PHYSIOLOGY

• Homeostasis is the basic principle of physiology • Homeostasis is the maintenance of a constant environment

COMPONENT OF A HOMEOSTASIS SYSTEM • Regulated variable is a variable to be kept constant. • Set point is the desired value of the regulated variable. • Sensors assess current status of the regulated variable. • Feedback controller compares current conditions with the set point. • Effector brings current status of regulated variable into line with the set point.

CHARACTERISTICS OF HOMEOSTASIS • Effectors may have opposing actions. • Negative feedback is the process that prevent change. • Positive feedback is the process that perpetuates change. • Feedforward control is outside stimuli that alter the normal feedback response.

COMMUNICATON IS AN ESSENTIAL ELEMENT OF A HOMEOSTATIC SYSTEM • Two languages of communication are chemical and electrical. • Characteristics of communication are distance, speed, distribution. The sensor has to communicate with the feedback controller and the feedback controller has to communicate with the effector. There are essentially two languages of communication. One is chemical and the other is electrical. These will be developed in later chapters.

Communication has several characteristics : 2. Distance : short vs long 3. Speed : fast vs slow 4. Distribution : focused vs diffuse

Communication occurs over distance as short as the environment surrounding a single cell. Cells can stimulate themselves, called autocrine stimulation, or their neighbor, called paracrine stimulation through the release of chemical agents. Communication can also occur over long distance, such as a nerve cell located in the spinal cord sending a process out to the end of the finger to stimulate a muscle cell.

Communication can be fast, again like nerve stimulation of a muscle cell or the electrical communication between cells during the heartbeat. And it can be slow. Slow communication occurs when the transmission of the chemical is determined by its distribution in the blood. The response to a hormone is intrinsically slower than that to nerve stimulation.

Finally, communication can be very focused, such as the activation of single muscle cells in the eye in order to focus on an object. And it can be diffuse, such as when epinephrine, released from the adrenal medulla when blood pressure falls, acts on the heart and the vasculature throughout the whole body.

COMMUNICATION BETWEEN CELLS – figure 1.2 Cells communicate with each other by mechanisms which include endocrine, paracrine and neurocrine actions. Endrocrine communication is through secretion of chemicals or hormones into the blood stream which then circulates to cells of target organs.

Paracrine is a cell to cell or local communication by adjacent cells via secretions which diffuse into the interstitial fluid. This is mediated by receptors.

In neurocrine or synaptic communication, the transmitter released at a nerve ending passes through a synapse to the communicating or post-synaptic cell.

Intercellular Communication Type

Description`

Means of Message Transmission

Local or General

Autocrine

Process by which cell produces subtance that regulates that cell or neighboting cells of same type

By diffusion in Locally diffese interstitial fluid

Examples

• Prostaglandine released by uterine tissue induce contractions of uterine smooth muscle • Prostaglandins released by bronchiolar smooth muscle induce vasodilation

Endocrine Process by By which cell circulating secretes blood regulatory substance directly into blood stream, which affects cells that maybe some distance away

General

•Anterior pituitary secretes prolactin, which travels via bloodstream to mammary glands to stimulate milk synthesis. •Pancreatic cells in islets of Langerhans secrete glucagon, insulin, somatostatin, and pancreatic polypeptide (pancreas has both exocrine and endocrine function)

Exocrine

Process by which cell delivers regulatory substances to an epithelial surface

Usually via a duct

Local

•Pancreatic acinar cells secrete digestive enxymes (eg, carboxypeptidase, pancreatic lipase, ribonuclease (trypsin) into pancreatic duct of Wirsung whish koins common bile duct to form ampulla of Vatex •Ducts sweat and salivary glands`

Neurl (Synaptic )

Process by which neurons release neuthansmitters across synaptic cleft to postynsaptic cells

Across sysnaptic cleft

Local

•At neuromuscular juntiong, nerve release AH which increases Na and K comtructor of musble membrane •This action causes info Na2 and produces depolarixing.

Nurocrine

Process by which Axonal neuron releases transport to regulatory bloodstream substances into blood stream to affect distant cells

General

• Hypotalamus releases hormone into bloodstream

Paracrine

Process by which 3y diffusin in cell secretes intertitialan regulatory hukum) subtance that diffuses inttto ECG to affact cells that are different from itselh`

Locally diffuse

Histamin released cells in wall aor thamh stimulates HL sectayn dengan pariental cellsof gastric glan.

Process of Intracellular Communication Sequence

Action

1

Agonist binds membrane receptor

2

• G protein is activated by binding GTP • Amplification allows one agonist complex to activate hundreds of effectors

3

• Activated G protein interacts with effector proteins to alter their activities •Effectors include enzymes, ion channels, and phospholipases

4

Effector proteins affect activities of second messengers (cAMP, cGMP, DAG, IP3)

5

Activity of second messenger alters activity of second messenger-dependent protein kinases (cAMPdependent protein kinases, cGMP-dependent protein kinases, protein kinase C, calmodulin-dependent protein kinase) or ion channels

6

Level of phosphorylation of enzyme or ion channel is altered

7

Final cellular response

AGE SPLuRge – Agonist, G Protein, Effector proteins, Second messengers, Protein kinases, level of phosphorylation, response

Intracellular Mediators Type

Description / Example

Second Messenger Cyclic Nucleotides (cAMP, cGMP)

• Vision depends on cGMP-gated Na+ channels present in plasma membranes of rods • When rhodopsin (receptor) is activated by light (stimulus), rhodopsin interacts with the G protein transducin • Activated transdusin interacts with cGMP phosphodiesterase, which increases eGMP and causes closing of cGMP- activated Na+ channels and hyperpolarization of photoreceptor cell

IP3 and DAG

• G protein activates agonist –receptor complex, which then cleaves phosphatidylinositol 4,5bisphosphate into IP3 and DAG • IP3 binds receptors on endoplasmic reticulum, leading to release of Ca2+ into cyctosol, which triggers cellular response • Immunosuppressant drug cyclosporine helps prevent transplant rejection by blocking this pathway.

Ca2+

Ca2+ calmodulin complex activates myosin lightchain kinase (a calmodulin-dependent protein kinase), which phosphorylates myosin, resulting in smooth muscle contraction.

Protein Kinases Protein Kinase

• Enzyme activated by second messenger that phosphorylates proteins on serine or threonine residues (protein phosphatase is enzyme that dephosphorylates proteins). • cAMP-dependent protein kinase phosphorylates rate-determining enzymes in glycogen metabolism • Ca2+ stimulates protein kinase C, which stimulates cell division and is involved in growth of tumor cells.

Protein Tyrosine Kinase • Membrane receptors that are themselves protein kinases • When agonist binds receptor, protein tyrosine kinase ohosphorylates protein substrates on tyrosine residues • Receptors for insulin and those for growth factors (epidermal growth factor, colonystimulating factor, fibrolast growth factor) are protein tyrosine kinases. • Uncontrolled protein-tyrosine kinases play major role in cell transformation and malignancy

G Proteins Heterotrimeric

• Nucleotide regulatory protein that aids in translation of signals between cells and helps modulate intracellular concentrations of second messengers. • In active state, acts as GTPase, hydrolyzing GTP toGDP • Adenylyl cyclase (enzyme that aids synthesis of cAMP) and cGMP phosphodiesterase (enzyme that breaks down cGMP) are modulated by G proteins. • Activation of phospholopase A2 by G protein leads to production of arachidonic acid

Monomeric

• Small G protein involved in protein synthesis, cell proliferation, neoplastic cell transformation and vesicle transport. • Ras like G protein regulate cell growth and differentiation • Rab-like G protein help target vesicles to membranes

Intercellular Communication By Chemical Mediators