Unit 3 - Drug Receptor Complex & ANS Flashcards
What is part of the CNS?
Brain and spinal cord
What is part of the peripheral nervous system?
Autonomic and somatic
What is part of the autonomic nervous system?
Parasympathetic (cranial/spinal & cranial/sacral) and sympathetic (spinal and thoraco/lumbar)
What is part of the somatic nervous system?
voluntary muscle movement (muscles, skin, body walls)
What are the two groups of somatic nerves?
Cranial and spinal
What does the sensory division of the ANS do?
Helps control BP, micturition (urination), defecation, and other activities that do not require conscious thought
Enteric nervous system
Autonomic, 2 networks or plexuses of neurons - myenteric plexus (digestive tract motility) and submucous plexus (sensing environment within lumen and regulating blood flow in GI and controlling epithelial cell function)
Ganglia of the CNS are
short axons of preganglionic neurons
Ganglia of the PNS are
close to the organs and long axons of pre-ganglionic neurons allowing organs to be stimulated individually
Which neurotransmitter is produced by the somatic motor system preganglionic axons?
Nicotinic (ACh)
Which neurotransmitter is produced from the autonomic preganglionic axons in the SNS and PNS?
Nicotinic ACh
Sympathetic postganglionic axon produces Adrenergic (Norepinephrine) to stimulate effects
Parasympathetic postganglionic axon produces Muscarinic (ACh)/cholinergic to stimulate effects
There is _____ neuron originating in the CNS for the somatic system
1
There are ___ neurons between the CNS and effector in the autonomic systems?
2
What type of axon in the somatic system is directly connected to the striated muscle?
one heavily myelinated
What type of axon in the autonomic systems are there?
Preganglionic = myelinated
Postganglionic = unmyelinated
True or false: Somatic nervous systems have ganglia
False
Where do the neurons connect in the autonomic systems?
Autonomic ganglia
True or false: All of the parasympathetic postganglionic fibers release ACh
True
True or false: None of the sympathetic postganglionic fibers release NE
False - most of them do; most of the sympathetic system utilizes NE
What is the effect of the sympathetic response on the eyes?
Pupil dilates to take in more light and allows for more vision in a stressful situation.
What is the effect of the parasympathetic response on the eyes?
Constricts pupils - not as much light needed and will not overstimulate the brain with too much light as dilation of pupils would
Function of the presynaptic cell
neuron that sends message
Function of the postsynaptic cell
cell that receives message
Function of the synaptic cleft
small gap that separates the presynaptic membrane and the postsynaptic membrane
What is the synapse?
area where a neuron communicates with another cell
What are the two types of synapses and how do they differ?
Electrical - direct physical contact between cells
Chemical - signal transmitted across a gap by chemical neurotransmitters
Describe the effect of an action potential on the synaptic terminal
- Action potential arrives and depolarizes synaptic terminal
- Calcium enters the terminal and triggers release of ACh
- ACh binds to receptors and depolarizes the postsynaptic membrane (initiation of action potential if threshold is reached at initial segment)
- ACh is removed by AChE & propagation of action potential (if generated)
Cholingeric receptors in the ANS
found in synapses of sympathetic and parasympathetic ganglia and in postgangliolic parasympathetic target organs
Nicotinic (found in PNS ganglia and leads to sympathetic and parasympathetic effects) and Muscarinic (found in all parasympathetic target organs)
Adrenergic receptors in the ANS
found only in sympathetic postganglionic target organs or effectors
a-receptors - stimulate contractions (a1 = contractions [BVs of viscera except heart], a2 = clotting [presynaptic receptors])
b-receptors - inhibit contractions except for heart contractility (b1 = increased HR and force of heart muscle + relaxation of heart BV; b2 = relaxes bronchioles, uterus, and all sympathetic target organs; b3 = increases lipolysis)
How does the stimulation of the parasympathetic response effect the heart?
If stimulated, ACh is released and binds to M2 receptors which acts to decrease the slope of pacemaker potential and decreases HR
How does the stimulation of the sympathetic response effect the heart?
postganglionic fivers release noradrenaline which act on B1 adrenoreceptors to increase the slope of pacemaker potential and increases HR and force of contraction
If all autonomic input was removed, which system would be dominant - Parasympathetic or sympathetic?
Sympathetic; increased HR and force of contraction
Which system would be dominant if a sympathectomy were done?
Parasympathetic; decreased HR and force of contraction
Atropine is a
muscarinic antagonist and constricts the pupil
Phenylephrine is an a1 ____________
agonist; dilates pupil
How does a G Protein-Linked Ion Channel work?
- Cadiac atrial muscarinic receptors (M2) is coupled with Gi protein
- This is connected to a potassium channel
- Agonist such as ACh is released
- ACh links to muscarinic cholinergic receptor
- Opens potassium channel
- Cell is hyperpolarized = negative (slows heart)
- Causes heart muscle to reach threshold more slowly
- Heart rate decreases
How does a G protein regulate a slow ligand-gated ion channel?
It opens or closes the channel
What happens when the Gs protein is stimulated
- Ligand binds to receptor, stimulates G protein
- Stimulates activation of enzyme adenylate cyclase
- Adenylate cyclase converts ATP into cAMP
- Gs leads to more intracellular cAMP
- cAMP is a second messenger which binds to receptrs in cell and activates inactive protein (kinase)
- Kinases activate inactive enzymes by adding PO4^3- (eventually, cAMP is broken down by phosphodiesterase)
- Inhibits smooth muscle contraction
What happens when the Gi protein is stimulated?
- Ligand binds to receptor
- Stimulates Gi protein
- Gi inhibits activation of adenylate cyclase
- Adenylate cyclase converts ATP into cyclic adenosine monophosphate (cAMP)
- Gi leads to less intracellular cAMP
- Less cAMP = less activation of kinase/phosphokinase A (PKA)
- Low PKA activity leaves Ca in sarcoplasm and allows calcium to initiate smooth-muscle contractions
- Calcium+Calmodulin combine to form complex
- Activates myosin light chain kinase and causes smooth muscle contraction
What kind of PG is Misoprostol?
E1
What is the mechanism of action of misoprostol?
- Synthetic PG E1 analog that stimulates PG E1 receptors on parietal cells in the stomach to reduce gastric acid secretion
- Mucus and bicarbonate secretion are also increased along with thickening of the mucosal bilayer so the mucosa can generate new cells.
- Misoprostol binds to smooth muscle cells in the uterine lining to increase the strength and frequency of contractions as well as degrade collagen and reduce cervical tone. (stimulates Gi protein)
What is the pathway of the Gq protein?
- First messenger hormone binds to receptor
- Gq protein activated
- Converts PIP2 into DAG and IP3
- IP3 (second messenger) moves to endoplasmic reticulum and causes the release of Ca2+
- Causes contraction
Which receptor does Ergonovine use?
alpha 1 adrenoreceptor
What is the pathway of ergonovine for stimulating contractions?
- Ergonovine binds to a1-receptor
- Gq protein stimulated
- Activates PLC which splits PIP2 into IP3 and DAG
- DAG opens the calcium channel in the membrane & extracellular Ca enters and cytoplasmic Ca increases
- IP3 opens Ca channel on sarcoplasmic reticulum
- Calcium enteres cytoplasm and binds to calmodulin
- Ca2+Calmodulin activates MLCK
- Contraction
What are first messengers?
Hormones or neurotransmitters
What do second messengers do?
Amplify effect, slow down the process, prolong the duration of the effect
How do G proteins amplify effects?
Gs and other G proteins activate their downstream effectors when bound by GTP and also have the ability to hydrolyze GTP.
Hydrolysis reaction inactivates the G protein, but can occur at a relatively slow rate, effectively amplifying the transduced signal by allowing the activated (GTP-bound) G protein to have a longer lifetime in the cell than the activated receptor itself (NE).
What kind of drugs require a second messenger?
lipophilic because they cannot pass the cell membrane
