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What chemical is secreted by the liver and binds to Ach in the plasma?
How many Ach molecules are required to open the nicotinic cholinergic receptor?
What is the rate limiting step and enzyme in the production of epinephrine?
- Tyrosine to DOPA
- Enzyme is tyrosine hydroxylase
List the epinephrine production pathway starting with Tyrosine along with enzymes
- Tyrosine DOPA : Tyrosine hydroxylase
- DOPA Dopamine : DOPA decarboxylase
- Dopamine Norepinephrine : Dopamine – beta – hydroxylase
- Norepinephrine Epinephrine : PMNT (Phyenylethanolamine-N-methyltransferase)
What is the result of Alpha-1 Adrenoceptor signaling?
- IP3 increases calcium and DAG increases protein kinase C
- Contracts smooth muscle
What is the result of Alpha-2 Adrenoceptor signaling?
- Decreases calcium entry into cells
- Increases potassium leaking
- Inhibits camp production
What is the result of Beta adrenergic signaling?
What type receptor is on all autonomic effectors?
What are metabotropic receptors?
What is a syncytium?
Cells connected by gap junctions
What is known as the cranio-sacral branch of the ANS?
Which has longer preganglionic nerves, the PNS or SNS?
What is the ratio of postganglionic to preganglionic nerves for the PNS?
1 to 1
Is the PNS or the SNS more selective at activating a single organ?
- The PNS
- Think of the SNS activating many organs at once during a fight or flight response, whereas the PNS has time to selectively activate only the organs that need to do work at that time
What is the ratio of postganglionic to preganglionic nerves for the SNS?
20-200 to 1
Where is the myenteric (Auerbach’s) plexus located and what is its function?
Between the longitudinal and circular smooth muscle layers. It regulates motility
Where is the submucous (Meissner’s) plexus? And what is its function?
Between the circular smooth muscle and the mucosa. It regulates mucosal absorption and secretion
What nervous inputs do the GI and smooth muscle and mucosa receive from the PNS and SNS?
PNS and SNS afferent as well as Efferent Preganglionic Parasympathetic and Efferent Postganglionic sympathetic
What is the primary neurotransmitter in neuromuscular junctions?
What type receptors do skeletal muscles express?
- Nicotinic cholinergic receptors
- (ligand-gated ion channels)
Does a muscle fiber exhibit all or none response or is it a graded response?
An individual muscle fiber exhibits an all or none response
What are the four NT that mediate chemical transmission at most peripheral synapses?
ACh, DA, NE, and Epi
What are the exceptions to the rule that Sympathetic postganglionic nerves release NE?
- Adrenal medulla – there are no postganglionic nerves, only preganglionic (release 80% epi, 20% NE)
- Renal, cerebral, and mesenteric blood vessels – dopamine (DA)
- Eccrine sweat glands – ACh
What is the rate limiting step in ACh synthesis?
The transport of choline into the cholinergic nerve terminal via the choline transporter using the energy of the Na+ gradient
Where is ACh synthesized? What enzyme is used?
- In the cytosol from choline and acetyl CoA
- Choline acetyltransferase (ChAT)
What type of transport gets ACh into synaptic vesicles?
- A combination of Secondary and Primary active transport
- The cell concentrates H+ in the vesicle using ATP, the H+ (Primary active transport)
- This gradient is then used to exchange H+ for ACh+ (Secondary active transport)
What signal initiates synaptic vesicle release?
Voltage gated Ca+2 channels depolarize allowing Ca+2 into the cell to trigger fusion of synaptic vesicles with the nerve terminal membrane
What is the difference between nicotinic and muscarinic cholinergic receptors?
- Nicotinic cholinergic receptors are ligand-gated ion channels
- Muscarinic cholinergic receptors are G-protein coupled receptors
Where are Nicotinic receptors found?
- All cells of autonomic ganglia
- Adrenal medulla
- Skeletal muscle
Where are muscarinic receptors found?
Where is the enzyme AChE found?
On the postsynaptic membrane
What subunits make up Neural nicotinic receptors?
2alpha and 3 beta subunits
What receptor subunits are in post-ganglionic autonomic neurons (nicotinic)?
- Two alpha3 and three beta4 (alpha3beta4 nicotinic receptors)
- Some alpha7
- What receptor subunits are in CNS neurons?
- Some alpha7
What receptor subunits are in fetal or denervated skeletal muscle?
What receptor subunits are in normal adult muscle?
Do autonomic nerve terminals exhibit a low or high safety factor of transmission?
What does the term “safety factor” mean with regard to nerve terminals?
- How much NT is released compared with how much was required to elicit a response
- If the safety factor is low, there is not enough NT released to elicit a response
- If the safety factor is high there is more than enough NT to elicit a response
Do skeletal muscle receptors exhibit a high or a low safety factor of transmission?
What occurs with stimulation of the M1, M3, or M5 receptors?
- Gqa activation of the Phospholipase C pathway (Ip3 and DAG)
- Stimulation of smooth muscles, exocrine glands, and autonomic neurons
What occurs with stimulation of the M2 or M4 receptors?
- Gia inhibition of adenylyl cyclase or activation of K+ channels and inhibition of Ca2+ channels for hyperpolarization
- Inhibits heart, autonomic nerve terminals, and autonomic neurons
What type receptors are adrenergic and dopaminergic receptors?
What stimulates Beta2 receptors?
Epi, but not NorEpi
What stimulates Beta1 receptors?
Epi and NorEpi
What receptors stimulate aqueuous humor production in the eye and renin secretion by the Juxtaglomerular cells of the kidney?
Beta 1 adrenergic
What receptor mediates sympathetic lipolysis and relaxation of GI smooth muscle?
Beta 3 adrenoceptors
Which dopaminergic receptors are exititory and cause relaxation and vasodilatation?
D 1, D 3, and D 5
Which dopaminergic receptors are inhibitory and cause hyperpolarization?
D 2 and D 4
What is the result if treatment of adrenergic agonists or antagonists is abruptly ended?
Because of the receptor up or down regulation that takes place, the patient is at risk for adverse cardiovascular responses
What is the precursor to NO and what enzyme is used?
L-arginine via nitric oxide synthase
What is the function of NO?
Activates guanylyl cyclase resulting in smooth muscle relaxation
What enzyme deactivates NO?
What receptors are found on the pupillary sphincter muscle to constrict the pupil in response to parasympathetic innervation?
M3 – which is also the receptor found in the ciliary body (which focuses the lens)
What receptors are found on the radial dilator muscle that increase pupil diameter in response to sympathetic stimulation?
How does the sympathetic system cause far vision?
Signals are sent to presynaptic alpha 2 receptors on parasympathetic nerve terminals which reduce parasympathetic tone resulting in relaxing of the ciliary muscle and flattening of the lens
What do muscarinic receptor agonists and AChE inhibitors accomplish for the eye and what are the side effects?
- Contract ciliary muscle, which opens the canal of Schlemm and reduces intraocular pressure
- Side effect is impaired far vision and miosis (pupillary constriction)
What has higher affinity for Epi and Norepi, Beta or alpha?
What do beta1 adrenoceptor antagonists and alpha2 adrenoceptor agonists do to intraocular pressure in glaucoma patients?
They inhibit aqueous humor formation and lower intraocular pressure
What governs tear production in lacrimal glands?
- M3 from parasympathetic produce tears
- The sympathetic system can stimulate blood vessel contraction via alpha 1 receptors on vascular SM which reduces tear production
- Circulating Epi or NE can also effect the alpha1 receptors resulting in protein-rich tears
- Circulating low levels of Epi stimulate Beta 2 receptors resulting in watery tear production
What is a telltale sign of overdose with either a muscarinic agonist or AChE inhibitor?
Profuse, watery tears
What is the result of parasympathetic stimulation of cardiac muscle and what receptor is responsible?
- M2 receptors
- The result is decreased amplitude and upstroke velocity of action potentials, and membrane hyperpolarization. This causes decreased HR (chronotropy), decreased conduction velocity (dromotropy), and contractile force (inotropy)
What receptors are responsible for stimulating cardiac muscle with circulating Epi and sympathetically stimulated NE?
- Beta 1
- Causes increased cardiac output
Does the vasculature receive parasympathetic input?
- No, sympathetic only
- However, there are M3 receptors that cause production of NO and vasodilation if exogenous M3 is added to the circulation.
Why does Epinephrine at low concentrations cause vasodilation?
Arteries express both alpha1 and beta2 receptors. The beta2 receptors have a higher affinity than alpha1 receptors, so at low concentrations the beta2 response is dominate.
What receptors on bronchiole smooth muscle cause contraction?
- Also M3 receptors on mucosal epithelial cells stimulate mucous secretion
How does the sympathetic system effect the respiratory smooth muscle and epithelium?
- Alpha2 receptors on the preganglionic parasympathetic nerves decrease parasympathetic tone
- Adrenal Epi causes bronchodilation via Beta2 receptors in smooth muscle
What effect does the parasympathetic system have on the gut?
Alpha3Beta4 Nn receptors generate fast EPSPs and action potentials which contract muscles of the gut wall and relax the sphincters
What three effect does the sympathetic system have on the gut?
- Postganglionic sympathetic nerves innervate Alpha2 receptors on preganglionic parasympathetic neurons to inhibit them, thus relaxing the gut
- GI sphincters are also innervated with alpha1 receptors to be contracted
- Circulating epi can cause relaxation via beta2 and beta 3
ACh released from submucous secretomotor neurons has an effect on histamine, gastrin, acid, and Somatostatin secretion. What is its effects on each and by what receptors?
- Histamine (M1) stimulate
- Gastrin (M3) stimulate
- Acid (M3) stimulate
- Somatostatin (M2) inhibit
What effects on submucous secretomotor neurons do parasympathetic and sympathetic stimulating have?
- Sympathetic inhibit via alpha 2
- Parasympathetic stimulate via alpha3beta4 Nn receptors
What effect does the parasympathetic system have on the islet of Langerhans cells?
Ach stimulates M3 receptors on the Beta cells to increase insulin production
What effect does the sympathetic system have on the islet of Langerhans cells?
- NE from sympathetic nerves or circulating Epi stimulate alpha1 receptors on alpha cells to produce glucagon and they stimulate alpha2 receptors on beta cells to inhibit insulin production
- Sympathetic nerves also vasoconstrict vessels which redistributes blood from beta to alpha cells and they inhibit parasympathetic nerves
What receptor is responsible for acute pancreatitis?
- M3 receptor
- This is hyperstimulized when gallstones occlude the common bile duct and pancreatic flow is slowed. Reflex parasympathetic responses attempt to increase pancreatic flow, causing acute pancreatitis
What receptor stimulates salivary secretion?
M3 from the parasympathetic system
Does the sympathetic system directly or indirectly inhibit salivary secretion?
Indirect via alpha 2 on parasympathetic and by vasoconstriction
What is the net effect on salivary glands of sympathetic stimulation?
Decreased secretion volume and increased viscosity
Does M3 receptor stimulation of salivary glands cause saliva production or does it inhibit?
Causes production of saliva
What does parasympathetic stimulation do to the detrusor muscle and trigone?
M3 receptors constrict the detrusor muscle and M2 receptors inhibit trigone contraction
What does sympathetic stimulation do to the detrusor and trigone?
- Trigone contracts via alpha1
- Detrusor relaxes due to alpha 2 stimulation to preganglionic parasympathetic
- Circulating EPI stimulates beta2 receptors to relax detrusor muscle
How would you treat an overactive bladder?
M3 receptor antagonist
When a pregnancy goes to term what causes the uterine contraction of labor?
A spike in maternal estrogen and oxytocin combined with a release of prostaglandins from fetal membranes
Why is exposure to NE, Epi, alpha 1 agonists, or drugs that release Epi or NE contraindicated in pregnancy?
- During pregnancy most autonomic innervation, especially SNS nerve terminals disappear
- This loss of terminals causes alpha 1 receptors to up-regulate
- Stimulation of up-regulated receptors can result in spontaneous labor
What drugs are used to arrest and prevent premature labor?
Beta 2 agonists
What drugs are used postpartum to restore uterine tone and to stop postpartum bleeding?
Alpha 1 agonists
How is erectile disfunction usually treated?
Inhibitors of cGMP phosphodiesterase
In a diabetic what effect would exogenous Beta 2 or alpha 1 agonists have on blood sugar?
They would raise blood sugar
What sympathetic receptors stimulate lipolysis?
Beta 3 adrenoceptors
How are eccrine sweat glands stimulated?
- M3 receptors from the sympathetic system (cholinergic)
- Critical for evaporative cooling in elevated temperatures
How are apocrine sweat glands stimulated?
- Noradrenergic sympathetics via alpha 1 receptors
- This is the type sweating that occurs during emotional stress
What causes Piloerection?
Noradrenergic stimulation via alpha 1 receptors