Communication,Integreted,Homeostasis

IEVA B. AKBAR

1. CELL-TO-CELL COMMUNICATIONThere are two basic physiological signals: chemical and electrical. Chemical signals are the basis for most communication within the body.There are three methods of cell-to-cell communication :Direct cytoplasmic transfer through gap junctionsLocal chemical communicationLong-distance communication

Gap junctions are protein channels that connect two adjacent cells. When they are open, ions and small molecules pass directly from one cell to the next.Local communication is accomplished by paracrines, chemicals that act on cells in the immediate vicinity of the cell that secreted the paracrine. A chemical that acts on the cell that secreted is called an autocrine. The action of paracrines and autocrines is limited by diffusion distance. Neuromodulators, cytokines and eicosanoids are paracrines.

Long-distance communication is accomplished by chemical neurocrine and electrical signals in the nervous system and by hormones in the endocrine system. Only cells that process receptors for the hormone will be target cells.Cytokines are regulatory molecules that control cell development, differentiation and the immune response. They function as both local and long-distance signals.

2. SIGNAL PATHWAYSChemical signals released by cells are called first messengers. First messengers bind to receptors and change intracellular effectors that direct the response.Protein phosphorylation by protein kinases is an important way to create a cellular response.Lipophilic signal molecules enter the cell and combine with cytoplasmic or nuclear receptors. Lipophobic signal molecules and some lipophilic molecules combine with membrane receptors.

Ligand-gatet ion channels open or close to create electrical signals.Signal transduction pathways use membrane proteins and intracellular second messenger molecules to translate information from the first messenger into an intracellular response.Many signal transduction pathways activate amplifier enzymes that create second messenger molecules.Signal pathways create intracellular cascades that amplify the original signal.

Integrin receptors link the extracellular matrix to the cytoskeleton.Receptor-enzymes activate protein kinases, such as tyrosine kinase, or the amplifier enzyme guanylyl cyclase that produces the second messenger cGMP.G protein linked to amplifier enzymes are not most prevalent signal transduction system. G protein-coupled receptors also alter ion channels.The G protein-adenylyl cyclase-cAMP-protein kinase A pathway is the most common pathway for protein and peptide hormones.

The amplifier enzyme phospholipase C creates two second messengers, IP3 and diacylglycerol. IP3 causes Ca2+ release from intracellular stores. Diacylglycerol activates protein kinase C.Calcium is an important signal molecule that binds to calmodulin to alter enzyme activity. It also binds to other cell proteins to alter movement and initiate exocytosis.Nitric oxide is a short-lived gaseous signal molecule that activates guanylyl cyclase directly.

3. MODULATION OF SIGNAL PATHWAYSThe response of a cell to a signal molecule is determined by the cells receptor for the signal.Receptor proteins exhibit specificity, competition and saturation.A receptor may have multiple ligands. Agonists mimic the action of a signal molecule. Antagonists block the signal pathway.Receptors come in related forms called isoforms. One ligand may have different effects when binding to different isoforms.

Cells exposed to abnormally high concentrations of a signal for a sustained period of time attempt to bring their response back to normal by decreasing the number of receptors or decreasing the binding affinity of the receptors. This is known as down-regulation of the receptors. Up-regulation is the opposite of down-regulation.Cells have mechanisms for terminating signal pathways.Many diseases have been linked to defect with various aspects of signal pathways, such as missing or defective receptors.

4. HOMEOSTASISWalter Cannon first described the four basic postulates of homeostasis :The nervous system plays an important role in maintaining homeostasis.Some parameters are under tonic control, which allows the parameter to be increased or decreased by a single signal.Other parameters are under antagonistic control, in which one hormone or neuron increases the parameter while another decreases it.Chemical signals can have different effects in different tissues of the body, depending on the type of receptor present at the target cell.

5. CONTROL PATHWAYS : RESPONSE AND FEEDBACK LOOPSThe simplest homeostatic control takes place at the tissue or cell level and is known as local control.In reflex control pathways, the decision that a response is needed is made away from the cell or tissue. A chemical or electrical signal is sent to the cell or tissue to initiate a response. Long-distance reflex pathways involve the nervous system, the endocrine system and cytokines.

Reflex pathways can be broken down into response loops and feedback loops. A response loop has an input signal, integration of the signal and an output signal. A stimulus begins the reflex when it is sensed by a receptor. The receptor is linked by a afferent pathway to an integrating center that decides on an appropriate response. An afferent pathway travels from the integrating center to an effector that carries out the appropriate response. These steps create a response loop.

In negative feedback, a homeostatic response is turned off when the response of the system opposes or removes the original stimulus.In positive feedback loops, the response reinforces the stimulus rather than decreasing it or removing it. This destabilizes the system until some intervention or event outside the feedback loop stops the response.Feedforward control allows the body to predict that a change is about to occur and start the response loop in anticipation of the change.

Apparently spontaneous reflexes that occur in a predictable manner are called biological rhythms. Those that coincide with light-dark cycles are called circadian rhythms.Nervous control is faster and more specific than endocrine control but is usually of shorter duration. Endocrine control is less specific and slower to start but is longer lasting and is usually amplified.Many reflex pathways are combinations of nervous and endocrine control mechanisms.