les agents provocateurs
neurotransmitters
1. acetylcholine (ACh)
2. norepinephrine (NE)
3. dopamine (D)
tyrosine and levodopa:
4. histamine (H)
hormones
1. epinephrine (Epi)
2. norepinephrine (NE)
enzyme degraders
1. cholinesterase (ACh-esterase)
2. monamine oxidase (MAO)
3. catechol-O-methyltransferase (COMT)
receptors
1. M1/M3 muscarinic
ligand: ACh
Gq activates phospholipase C
release of IP3 and DAG
increased Ca2+
M1: CNS, ganglia, parietal cell secretion
M3: contraction of smooth muscle/exocrine gland secretion
2. M2 muscarinic
ligand: ACh
dissociation of inhibitory Gi
inhibition of adenylyl cyclase
mediates closing of Ca2+ channels
slows heart rate
atropine is an antagonist
— M4 muscarinic
activation of inhibitory Gi
found in CNS
neostriatum: caudate nucleus & putamen
— M5 muscarinic
coupled to Gq
release of IP3
found in CNS
substantia nigra
3. N1 nicotinic ligand-gated ion channel (Nn)
ligand: ACh
subunits: α3,α5,α7,β2,β4
rapid opening of Na+ channel
depolarization of ganglia cells
trimethaphan is an antagonist
4. N2 nicotinic ligand-gated ion channel (Nm)
ligand: ACh
subunits: α1,β1,δ,γ(ε)
rapid opening of Na+ channel
depolarization of skeletal muscle
tubocurarine is an antagonist
— nicotinic ligand-gated ion channels in the CNS
— dihydro-β-erythroidine is an antagonist
subunits: α3,α4,β2,β4
most common
— α-bungarotoxin is an antagonist
subunits: α7,α8,α9
5. alpha1 (α1) adrenergic
ligand: NE or Epi
Gq activates phospholipase C or A2
release of IP3 and DAG
increased Ca2+
contraction of smooth muscle
6. alpha2 (α2) adrenergic
ligand: NE or Epi
dissociation of inhibitory Gi
inhibition of adenylyl cyclase
decrease activity
function in some presynaptic terminals & pancreatic islets
7. beta1 (β1) adrenergic
ligand: NE or Epi
activation of stimulatory Gs
activation of adenylyl cyclase
increased cardiac activity
8. beta2 (β2) adrenergic
ligand: Epi (NE much less so)
activation of stimulatory Gs
activation of adenylyl cyclase
relaxation or dilation of smooth muscle
— beta3 (β3) adrenergic
ligand: Epi or NE
activation of stimulatory Gs
activation of adenylyl cyclase
promotes lipolysis in adipocytes
9. D1 dopaminergic
ligand: dopamine
activation of stimulatory Gs
activation of adenylyl cyclase
vasodilatation in kidney
— D2 dopaminergic
reduces cAMP ⇒ inibitory
↑ in schizophrenia & Tardive dysphrenia
two subtypes
— D3 dopaminergic
reduces cAMP ⇒ inibitory
— D4 dopaminergic
reduces cAMP ⇒ inibitory
numerous subtypes
selective D4 agonist for Parkinsonism with fewer side effects
— D5 dopaminergic
increases cAMP ⇒ excitatory
10. histamine
H1: linked to Gq with stimulation of phospholipase C activity, and the subsequent contraction of smooth muscle (bronchiolar). Also in CNS.
H2: linked to Gs with stimulation of adenylyl cyclase activity, and in the stomach leads to release of acid into the lumen
H3: linked to Gi with decrease in adenylyl cyclase activity. The signal transduction pattern remains to be identified; it functions, however, to reduce the release of many neurotransmitters, including histamine itself.
H4: linked to G? with ????? activity. It is highly expressed in bone marrow and white blood cells (particularly eosinophils) and regulates zymosan-induced neutrophil release from bone marrow.
| CNS | preganglionic fiber | ganglion | postganglionic fiber | effector |
|---|---|---|---|---|
|
brain stem parasympathetic |
long | ACh .. N | short |
ACh .. M cardiac & smooth muscle gland cells nerve terminals |
| spinal cord sympathetic |
short | long |
ACh .. M sweat glands |
|
|
NE .. α, β cardiac & smooth muscle gland cells nerve terminals |
||||
|
D .. D1 renal vascular smooth muscle |
||||
| ACh .. N adrenal medulla |
hormonal release of Epi & NE | |||
| spinal cord parasympathetic |
long | ACh .. N | short |
ACh .. M smooth muscle gland cells |
| spinal cord voluntary motor nerve |
long |
ACh .. N somatic skeletal muscle |
||
two-neuron motor chain
CNS
preganglionic fibers
ganglion
postganglionic fibers
effector
sympathetic
functions
so-called “fight–or–flight” system
involves the E activities
excercise
blood flow to organs is ↓
blood flow to muscles is ↑
excitement
emergency
heart rate ↑
breathing is deepened and rate ↑
skin is cold and sweaty
pupils dilate
embarrassment
blood flow to facial vessels is ↑
general design
outflow is from spinal nn T1 – L2
sympathetic chain ganglia
collateral ganglia
adrenergic receptors
alpha (α)
excitatory response in effector organ
beta
β1
excitatory
β2
inhibitory
parasympathetic
functions
the “relaxed” system
involves the D activities
digestion
blood flow to organs is ↑
heart rate and blood pressure are ↓
repiratory rates are ↓
skin is warm
pupils are constricted
defecation
diuresis
general design
outflow is from cranial nerves (III, VII, IX, and X) and sacral spinal nerves (S2 – S4)
terminal ganglia
enteric nervous system
cholinergic receptors
nicotinic
autonomic ganglia
muscarinic
effector cells
atropine is selective muscarinic blocker
release of neurotransmitter by varicosities
dual innervation of most visceral organs
sympathetic and parasympathetic tone
sympathetic and parasympathetic dominance
control levels of autonomic activities
spinal reflexes
urination, defecation, erection
medulla
cardiovascular, respiratory, digestive centers
hypothalamus
integration of autonomic, somatic, endocrine responses
frontal cortex
emotional autonomic responses
motor neurons act as final common pathway
end plate potential (EPP) is larger than EPSP, thus resulting in action potential
acetylcholinesterase
short duration of ACh binding: ~10–9 sec
vulnerabilities of the NMJ
black widow spider venom
causes explosive release of ACh
botulinum toxin
blocks release of ACh (~10–4 mg is lethal)
curare
competitively binds with ACh receptor
organophosphates
irreversibly inhibit AChE
| Questions for thought | ||
|---|---|---|
| 1. | Which autonomic fibers release acetylcholine? Which release norephinephrine? | |
| 2. | Describe the meaning and importance of sympathetic tone and parasympathetic tone. | |
| 3. | List the receptor subtypes for ACh and NE, and note the major sites where each type is found. | |
| 4. | Explain the hierarchy of autonomic nervous system control. | |
| 5. | Describe what is meant by the terms chronotropy and inotropy and applied to the heart and how these can be manipulated by the autonomic nervous system. | |
| 6. | Explain, with examples, the vulneribilites of the neuromuscular junction. | |
| 7. | Dr. Martin is suffering from a condition known as V-tach (ventricular tachycardia), in which the heart beats too quickly. Would an α-blocker or β-blocker be appropriate therapy, and why? | |
| Other questions to test your knowledge | ||
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[ Anatomy & Physiology 1 syllabus ][
Anatomy & Physiology 2 syllabus ] [ Page created 1999-08-02 ][ Last updated 2008-07-16 ] [ Questions about this lecture? E-mail me ] |