Physiology second semester first year summary. Membrane and Muscle Physiology summarized in full depth, with examples. All study Units are included in the summary.
, Chapter 5
Study Unit 1.1
Control of cells through chemical messengers
5.1 Receptors
-Once a cell detects signal, a mechanism is required to transduce that signal into a physiologically meaningful response.
Receptor
-The binding of a messenger to a receptor changes the conformation of the receptor, which activates it. (Section 5.2)
activation
-This initiates a sequence of events in the cell leading to the cell's response to that messenger - signal transduction
-The "signal" is the receptor activation.
-Transduction is the process by which a stimulus is transformed into a response.
Types of receptors
-Nature of receptors that bind intercellular chemical messengers: they are proteins or glycoproteins located in either the cel's plasma
membrane or inside the cell ( in the cytosol or nucleus.
¥ The plasma membrane is a more common location be cause very large numbers of messengers are water soluble thus cannot
diffuse through a lipid rich plasma membrane
-A plasma membrane receptor has hydrophobic segments within the membrane and other hydrophilic
segments extending out of the membrane into the extracellular fluid & others into the intracellular
-Arriving chemical messengers bind to the extracellular parts of the receptor and the
intracellular regions of the receptor are involved in signal transduction events.
Intracellular receptor
-Are not located in membranes but exist in either the cytosol or the cell nucleus & have a very different structure.
Like plasma membrane receptors, they have a segment that binds the messenger and other segments that act as
regulatory sites.
-Segments that bind to DNA,segments that
serve as regulatory sites
,Interactions between receptors and ligands
4 major features: specificity, affinity, saturation, and competition.
Specificity Example: lock and key
-Binding of a chemical messenger to its receptor initiates the events leading to the cellÕs response.
-A protein binds a particular ligand & not others if its binding site
for that ligand is specific.
-Only certain cell types express the specific receptor required to
bind a given chemical messenger.
Example: the neurotransmitter norepinephrine causes muscle cells of the heart to contract faster
but via the same type of receptor regulates certain aspects of behavior by acting as neurons of
the brain.
Affinity
-A receptor with high affinity will bind at lower concentrations of a messenger than will a receptor of low affinity.
-Receptors with high affinity for a ligand (messenger) require much less of the ligand to become activated.
Saturation
-A cell's response to a messenger increases as the extracellular
concentration of the messenger increase because the number of
receptors occupied by messenger molecules increases.
-There is a finite number of receptors and they become saturated at some point, cell response cannot increase anymore and has limits
¥When a receptors are occupied, they are fully saturated
Competition
Antagonist- is a compound that blocks the action of a chemical
messenger.
When an antagonist works by competing with a chemical
messenger for itÕs binding site is known as competitive antagonist
Example: beta-adrenergic receptor blocker, beta blockers compete with epinephrine & norepinephrine to bind to one of their receptors
-Because epinephrine & norepinephrine normally act to increase blood pressure, beta-blockers tend to decrease blood pressure by acting
as competitive antagonist.
,Example: antihistamines are useful in treating allergic symptoms brought on due to excess histamine secretion from cells known as mast
cells- certain antihistamines are competitive antagonists that block histamine from binding to its receptors on mast cells & triggering an
allergic response.
-Agonist: are used therapeutically to mimic the messengerÕs actions.
Example: common decongestant drugs phenylephrine & oxymetazoline mimic the action of epinephrine on a related but different subtype
of receptors called alpha-adrenergic receptors in blood vessels.
-When alpha- adrenergic receptors are activated, the smooth muscles of inflamed dilated blood vessels in the nose contract resulting in
narrowing of the those vessels - this helps open the nasal passages and decrease fluid leakage from blood vessels.
Regulation of receptors
-Down regulation: is a decrease in the total number of target cell receptors for a given messenger; may occur in response to chronic
high extracellular concentration of the messenger.
¥Has the effect of reducing the target cellsÕ responsiveness to frequent or intense stimulation by a messenger- thus desensitising
them- represents a local negative feedback mechanism. Lysosomes break the receptor up- degrade the receptor.
¥Internalisation is the main mechanism of down-regulation of plasma membrane receptors by receptor-mediated endocytosis
¥The binding of a messenger to its receptor can stimulate the internalisation of the complex - the messenger-receptor complex is
taken into the cell by receptor mediated endocytosis thus increasing the receptor degradation inside the cell.
-Up-regulation: is an increase in the total number of target-cell receptors for a given messenger; may occur in response to a chronic low
extracellular concentration of the messenger
¥Cells exposed for a prolonged period to very low concentrations of a messenger may come to have many more receptors for that
messenger- developing increased sensitivity to it.
¥The greater the number of receptors available to bind a ligand, the greater the likelihood that such binding will occur.
¥Receptor proteins are stored in vesicles
Example: addiction, receptors are down-regulated and then you continue to use more and more quantities
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