Compare and contrast Sympathetic and Parasympathetic nervous systems
Long preganglionic/short postganglionic
Ganglion normally in organ being innervated
Cholinergic/Nicotinic (Ionotropic) receptor at ganglion
Cholinergic/Muscarinic (g protein coupled) receptor (M1, M2, M3) at effector site
Short preganglionic/Long postganglionic
Multiple axons after ganglion
Cholinergic/Nicotinic (Ionotropic) receptor at ganglion
Adrenergic(g protein coupled) receptor (A1, A2, B1, B2) at effector site
Compare and contrast the somatic and autonomic nervous systems
Somatic Nervous System-Anatomical
a) Ganglia outside CNS=None
b) Pathway from CNS- Effector Organ=Uninterrupted
d) Peripheral plexus=None
e) Reflex Arc=Spinal cord and brain stem
Autonomic Nervous System
a) Ganglia outside CNS=YES: Paravertebral Prevertebral, Intramural
b) Pathway from CNS- Effector Organ=interrupted
c) Fibers=Preganglionic-myelinated; Postganglionic-unmyelinated
d) Peripheral plexus=Fibers branch and form a network
e) Reflex Arc=Spinal cord and brain stem
a) Peripheral Effect-Excitation
b) After Denervation-Paralysis (atrophy)
c) Control Environment-Adjusts body to external environment
a) Peripheral Effect-Excitation or Inhibition
b) After Denervation-No Paralysis
c) Control Environment-Regulation of internal environment
a) Neurotransmitter-Acetylcholine & norepinephrine
b) Co-transmitters-Vasoactive intestinal peptide (VIP-parasympathetic), Neuropeptide Y (Sympathetic), ATP (Sympathetic and Parasympathetic)
What are some exceptions to the rule in the sympathetic nervous system?
Eccrine Sweat Glands- The postganglionic neurons that are involved with stress related excretion release use NE. Those involved with thermoregulation release use ACh
Kidneys-Postganglionic neurons to the smooth muscle of the renal vascular bed release dopamine
Adrenal gland-Pregangl. neurons do not synapse in paravertebral symp ganglion. They synapse directly with adrenal gland which has nicotinic receptors. Adrenal glands release NE and epi into circulation (no postganglionic).
What are primary afferent nerves like? Enteric afferent nerves? Which ganglion do enteric afferents use that go to the spinal cord? and that go to cranial nerves?
Primary afferent-Bipolar, go all the way from organ into CNS.
Enteric afferent-Synapse in a ganglion before reaching CNS
Ganglions-Spinal (Dorsal Root), Cranial (Petrosal, Nodose, Geniculate)
Where is myenteric plexus located? What does it do? What is another name for it? What is it like? Same questions for submucosal plexus?
Myenteric-Large, between the two muscle layers in the gut. Found throughout GI tract. Auerbachs plexus. Peristalsis and Motility
Submucosal-Small, Located closer to lumen, not in stomach or esophagus. Stimulate secretion
What are the sensory neurons in the enteric nervous system? What are the effector systems? How is it connected with the CNS? How does it use interneurons and motor neurons w/o CNS? What are the Enteric Pacemakers?
Sensory neurons-Chemoreceptors, mechanoreceptors, thermoreceptors.
Not using the CNS, these sensory neurons relay information to interneurons (reflex circuits and motor programs) which send signals to motor neurons to either excite or inhibit the effector systems.
Also, the Sensory neurons can send signals to the CNS (Autonomic) which sends signals to the interneurons to cause the same actions.
Effector systems-Muscle, secretory epithelium, Inflammatory cells, endocrine cells, vasculature
Enteric Pacemakers-Interstitial cell of Cajal (ICC)-Not neural or glial but in between-mediates neurotransmission from nerves to bowel SM cells (pacemaker)
What are 4 inputs to the NTS? What is the output? What are 2 general options of what can happen once a visceral afferent signal reaches the Nucleus Tractus Solitarius (NTS)? What kinds of signals does the area postrema receive? What are two possible general responses of central integration?
Inputs to NTS-Autonomic Sensory nerves, Ascending spinal pathways, nuclei of the brain, area postrema
Output of NTS-Various nuclei in the brain that can carry out the correct response.
Signal to NTS can go down into a reflex pathway (autonomic output) or it can go up for central integration. With central integration, two possible options are the limbic system-->behavioral response and endocrine system-->hormonal response
Area postrema receives info concerning plasma electrolytes, hormones, and CSF chemicals
What are 3 examples of co-transmission and neuromodulation?
Presynaptic inhibition-signal sent, negative feedback sent to autoreceptors on same neuron
Heterotropic presynaptic inhibition-NT from nearby neuron gives negative feedback on heteroreceptor
Postsynaptic synergism-Two different NTs lead to a stronger signal.
What 3 things are autonomically effected in the eye? What is the sympathetic effect and the receptor type? What is the parasympathetic effect and the receptor type?
Radial Muscle (outer) and Sphincter/Circular Muscle (inner), iris
Symp: contraction radial muscle-->pupil dilation (mydriasis)++, A1
Parasymp: contraction of circular muscle-->smaller pupil (Miosis)+++, M3/M2
Symp: Relaxation for far vision, B2
Parasymp: contraction for near vision+++, M3/M2
Symp: Secretion+, A
Parasymp: Secretion+++, M3/M2
What 5 things are autonomically effected in the heart? What is the sympathetic effect and the receptor type? What is the parasympathetic effect and the receptor type? What are some terms to know concerning the heart?
Symp: Increase in heart rate (positive cronotropic)++, B1>B2
Parasymp: Decrease in heart rate+++, M2>>M3
Symp: Increase in contractility (Inotropic) and conduction velocity++, B1>B2
Parasymp: Decrease in contractility and contractility and shortened AP Duration++, M2>>M3
Symp: Increase in automaticity and conduction velocity (dronotropic)++, B1>B2
Parasymp: Decrease in conduction velocity, AV block+++, M2>>M3
Symp: Increase in automaticity and conduction velocity, B1>B2
Parasymp: Little effect, M2>>M3
Symp: Increase in contractility, conduction velocity, automaticity, and rate of idioventricular pacemakers+++, B1>B2
Parasymp: little effect
Dronotropic-conduction velocity, inotropic-contractility, chronotropic-heart rate, bradycardia (slow heart rate), tachycardia (fast heart rate), atrial flutter (even faster heart rate), fibrillation (lack of coordination of muscles), ventricular fibrillation leads to death.
What are 2 bold statements concerning autonomic nervous system and blood vessels? Are there parasympathetic (muscarinic receptors in blood vessels? Are they innervated? What are 2 examples of them being innervated? What does this mean concerning medications? Where are the muscarinic receptors located? What effect does it have when they are stimulated? How does NO prevent constriction? Which 7 arteries/arterioles are innervated by autonomic? What does symp do with which receptor? What does parasymp do with which receptor? Same with veins?
Every blood vessel has a sympathetic receptor; it is mainly just controlled by sympathetics. Also, every alpha receptor in a blood vessel will cause contraction of SM and thus vasoconstriction-->increase BP
There are parasymp receptors in blood vessels in the endothelium that oppose the symp but they are not innervated. however, they are able to be stimulated by medication. When this happens, they release NO which activates guanylate cyclase which creates cGMP which prevents myosin-P/actin binding which prevents muscle contraction leading to dilation. Vessels in erectile tissue and salivary gland are innervated by parasymp nerves leading to dilation.
Coronary, Viscera, Skin, and Brain
Parasymp: No effect
symp: dilation, B2
Parasymp: No effect
Erectile Tissue and salivary gland
Symp: Constriction, A
Parasymp: dilation, M3
symp: constriction, A; Dilation, B2
Parasymp: No effect
What 3 things are autonomically effected in the lung? What is the sympathetic effect and the receptor type? What is the parasympathetic effect and the receptor type?
Tracheal and bronchial SM
Symp: Relaxation (open airway), B2
Parasymp: contraction (constrict airway), M2=M3
Symp: not important
Parasymp: Stimulation, M3/M2
Symp: Inhibition, b2; stimulation, a1
parasymp: stimulation, M2/M3
What is the GI tract mainly controlled by? What 3 things are autonomically effected in the GI tract (both stomach and intestine? What is the sympathetic effect and the receptor type? What is the parasympathetic effect and the receptor type?
Mainly controlled by parasymp not symp
Motility and tone
Symp: decrease+, all of them
Parasymp: Increase+++, M2=M3
Symp: contraction+, A1
Symp: Inhibition, A2
Parasymp: Stimulation++, M3/M2
What effect does the autonomic system have on gallbladder/ducts? What is the sympathetic effect and the receptor type? What is the parasympathetic effect and the receptor type?
Symp: Relaxation+, B2
Parasymp: contraction+, M
Which branch of ANS causes Renin secretion in kidney? Which receptor is used? How does the angiotensin pathway work?
JG cells are stimulated to secrete renin. Renin causes the conversion of Angiotensinogen to angiotensin I which is converted by ACE to angiotensin II which causes vasocontriction, release of aldosterone (prevents release of water and sodium-->increase BP), and increase release of NE (more vasoconstriction).
Symp: increase++, B1
Parasymp: no innervation
What 2 things are autonomically effected in the urinary bladder? What is the sympathetic effect and the receptor type? What is the parasympathetic effect and the receptor type?
Symp: relaxation++, B2
Parasymp: contraction+++, M3>M2
Trigone and sphincter:
Symp: contraction++, A1
Parasymp: relaxation, M3>M2
How is the uterus affects by SANS and PANS? Receptors?
Symp: Relaxation, B2
How is the male sex organs affects by SANS and PANS? Receptors?
Symp: ejaculation++, A1
Parasymp: erection+++, M3
What 3 things are effected by ANS in skin? Which branch are they affected by? Receptors
Apocrine Sweat glands (milky/stinky)
Symp: localized secreation+, A1
Eccrine sweat glands
Symp: Generalized Secretion+++, M3/M2
What are the effects of ANS on spleen? Which branch? Receptors?
Symp: contraction+++, A1; relaxation, B2
How are skel muscle, the liver, pancreatic Beta cells, and fat cells affected by ANS? Receptors?
Symp: increaseed contractility, glycogenolysis, K+ uptake, B2
Symp: glycogenolysis, A1; Gluconeogenesis, B2
Pancreas beta cells
Symp: Decreased secretion+++, A2; Increased secretion, B2
Parasymp: Secretion++, M3/M2
Symp: Lipolysis+++ (thermogenesis), mainly B2 ; inhibition of lipolysis, A2
Give an overview of the events in the lifecycle of acetylcholine.
Choline is transported into axon terminal by a carrier. Choline and Acetyl CoA are transformed into acetylcholine by Choline Acetyltransferase. ACh is put into a vesicle by a carrier. ACh is stored in a vesicle along with other possible NTs (ATP, VIP). When the neuron is depolarized, Calcium enters the axon terminal and causes the vesicle to fuse and release the NTs. Once released, ACh can interact with muscarinic receptors or nicotinic receptors. ACh can also act on presynaptic muscarinic or nicotinic receptors (autoreceptors) to modify its own release. ACh is deactivated by metabolism to choline and acetate by AChE.
What are the two main types of cholinergic receptors? What are the subgroups and subtypes of these? What are some characteristics of the groups and subgroups? How do they work? What muscarinic receptor is primarily found in most smooth muscles and glands? Which is found in the heart?
Nicotinic-ganglionic, skel muscle, neuronal CNS:ionotropic, 5 subunits
Muscarinic-M1/M3/M5 and M2/M4: g=protein coupled
M1/M3/M5-Gq-activation of PLC (increased IP3 and DAG)-->increased PKC and Calcium-->depolarization-->contraction
M2/M4-Gi-Inhibition of Aden Cycl-->less cAMP; activation of K+ channels; Both lead to hyperpolarization and inhibition--->relaxation of muscle.
M3 is primarily found in most SM and glands (contraction). M2 is primarily found in heart (relaxation).
What are the cholinergic receptors at ganglions, effector sites, and neuromuscular junctions? What is their primary classification? What are some agonists for each? What are some antagonists for each?
Postganglionic-Muscarinic (atropine sensitive)
Agonists: ACh, methacholine, pilocarpine
Antagonists:Atropine, Scopolamine, Methantheline
Ganglionic-Nicotinic I (hexamethonium sensitive)-does most of the transmitting AND Muscarinic (atropine senstive)-same agonists as other muscarinic, no methantheline
Agonists: ACh, Nicotine, succinylcholine
Antagonists: Hexamethonium, Mecamylamine, Trimethaphan, Curare
Neuromuscular-Nicotinic II (curare senstive)
Agonist: ACh, Nicotine
Antagonist: Curare, Succinylcholine, Pancuronium
What are 5 presynaptic mechanisms by which we can manipulate the lifecycle of acetylecholine? What is the representative drug that does each? What is the effect? Which are used clinically?
Inhibition of Vesicular Uptake-Vesamicol-Depletion of ACh
Inhibitors of ACh Release-Botulinus Toxin-Anticholinergic
Muscarinic Autoreceptors--->less calcium--->inhibit ACh release-Ach-Anticholinergic
Block of choline transport system-Hemicholinium-Depletion of ACh
Inhibitor of pyruvate dehydrogenase-bromopyrute-depletion of ACh (no acetyl Coa)
Only the ones that inhibit ACh release are used clinically
What are 5 postsynaptic mechanisms by which we can manipulate the lifecycle of acetylecholine? What is the representative drug that does each? What is the effect? Which are used clinically?
Nicotinic antagonist-Trimethapan and hexamethonium
Muscarinic antagonist-atropine-cholinergic blockade
What enzymes are responsible for the conversion of tyrosine to epinephrine? Where are they located? What is their substrate specificity if any? What is their function? Any other characteristics of them?
Tyrosine Hydroxylase-Widespread, in symp. nerves-specific for l-tyrosine-converts tyrosine to dopa-it is the rate limiting step so inhibition of it can lead to depletion of NE
AAADC-Widespread, in symp nerves-non specific-converts dopa to dopamine-inhibition does not alter tissue NE or E appreciably
DBH-Widespread, in symp nerves=non specific-converts dopamine to NE-inhibition can decrease NE/E levels
PNMT-Largely in adrenal gland-non specific-converts NE to E-inhibition leasd to decrease in adrenal catecholamines; it is under control of glucocorticoid
What are heteroreceptors and autoreceptors? Which muscarinic and andrenergic receptors function as hetero and autoreceptors?
ACh can inhibit the release of ACh from its own cell or it can inhibit the release of NE from a nearby cell (heteroreceptors). Both the autoreceptor and heteroreceptor are A2 adrenergic receptors.
The same thing can happen with NE and the autoreceptor and heteroreceptor are M2.
What happens with the NTs at the symp. axon terminal, specifically the events of the life cycle of NE?
tyrosine enters the axon terminal, is converted to Dopa by TH, which is converted to dopamine by AAADC, which enters into a vesicle. In the vesicle, it is converted to NE by DBH. NPY and ATP also enter into the vesicle-they tend to cause the same effect as NE or enhance its effect. Polarization leads to more calcium in the terminal which leads to fusion of vesicle with plasma membrane and release of the NTs. NE can then bind to receptors on postsynaptic cell or can bind to autoreceptors or be cleared. It is cleared by reupatke back into adrenergic neuron. There, it can enter into another vesicle or be metabolized by MAO. A smaller amount is taken into postsynaptic tissue where it is metabolized by MAO or COMT. An even smaller amt. diffuses into circulation where it is metabolized by COMT and MAO during passage through liver or kidney.
What is the occurence of MAO and COMT? What is their subcellular distribution? What is their substrate specificity and function? What other characteristics do they have? How do they work together to metabolize catecholamines?
Widespread neuronal; adrenal medulla; extra neuronal (large amts in brain and liver).
Mostly in mitochondria
Non-specific-oxidizes all monoamines
Regulates intraneuronal NE levels-
Inhibition leads to increased tissue CA levels
Widespread; mainly liver, kidney; extraneuronal; adrenal medulla
Specific for Catechols, o methylates them
regulates extraneuronal and circulating CA levels
They work together to metabolize E and NE to VMA. They can be o methylated first or oxidized first and the result is the same.
What are the adrenergic receptors we're responsible for knowing? What is their pathway?
Alpha1-Gq-->activation of PLC-->increase in IP3 and DAG--->increased calcium--->contraction
Alpha2-Gi-Inhibition of Aden cyclase--->less cAMP--->inhibition of PKA
Beta receptors 1 and 2-Gs-Activation of Aden Cyclase-->increase cAMP-->activation of PKA