Documentos de Académico
Documentos de Profesional
Documentos de Cultura
Muscle
Tina K. Machu, Ph.D.
Objectives
1. Describe the basic peripheral neural pathways of the parasympathetic
and sympathetic autonomic nervous systems, listing:
the neurotransmitter released at ganglia and neuroeffector junctions
the receptor type mediating the effects on postganglionic neurons or
effector organ function.
2. Describe the basic structural features and signal transduction
mechanisms of nicotinic and muscarinic cholinergic receptors and
alpha and beta adrenergic receptors.
3. Describe the major steps in cholinergic and adrenergic
neurotransmission.
4. List the major physiological effects regulated by the parasympathetic
and sympathetic nervous systems with particular attention to smooth
muscle responses.
Objectives
5. Describe the effects of the following drug prototypes on smooth muscle
function:
Muscarinic agonists acetylcholine, muscarine, bethanechol
Muscarinic antagonists atropine, ipratropium bromide
Alpha adrenergic agonists norepinephrine, epinephrine, phenylephrine
Alpha adrenergic antagonists phentolamine
Beta adrenergic agonists norepinephrine, epinephrine, albuterol
Beta adrenergic antagonists propranolol
Drug List
Muscarinic Receptor Agonists:
Acetylcholine, Muscarine, Bethanechol
Key Terms
Cholinergic refers to acetylcholine (ACh)
Nerves that release ACh are cholinergic
Receptors activated by ACh are cholinergic
Nicotinic and muscarinic
adrenergic
Autonomic
Nervous
System
Steps in
Acetylcholine
Neurotransmission
Adrenergic receptors
Alpha adrenergic receptors
or M2, M4
Muscarinic
receptor
Parasympathetic System
Discrete, localized discharge
Rest & Digest
Sympathetic System
Preganglionic sympathetic neurons are cholinergic
(ACh)
Postganglionic sympathetic neurons are adrenergic
(NE)
Exception is sympathetic neurons to sweat glands these
sympathetic neurons are cholinergic, i.e., release Ach
Exception is specialized neurons innervating afferent arterioles of
kidney these neurons release dopamine which causes relaxation
of the vascular smooth muscle & vasodilation by activating D1
dopamine receptors
Sympathetic System
Fight or Flight (NE & Epi)
Heart rate increases, blood pressure rises
RBCs poured into blood from spleen to carry more
O2
Blood flow shifted from skin and splanchnic region
to skeletal muscles
Blood glucose rises
Bronchioles and pupils dilate
Brain receives signals to facilitate purposeful
responses & to imprint the event in memory
Therapeutic uses of
cholinoceptor activating drugs
Bethanechol: (prototype)
Postoperative or neurogenic urinary
retention
Postoperative atonic bowel without
obstruction
Atropine Effects
Heart:
Eye:
tachycardia
Bronchial:
GI Tract:
Urinary:
Glands
Bronchodilators:
Ipratropium bromide
A muscarinic receptor antagonist
If given parenterally, effects are like atropine
But, only given as inhaled aerosol
few side effects, even when swallowed because is poorly
absorbed from GI and does not cross into brain
poor diffusion across membranes
Responses
Responses
Responses to Adrenergic and Cholinergic Nerve Stimulation
Organ or tissue
function
Predominant
adrenoceptor
type
Bronchial smooth 2
muscle
Blood vessels
Cutaneous
1
Visceral
1
Pulmonary
1
Skeletal muscle 1, 2
-Coronary
1,
Cerebral
Veins
1
1
Sympathetic/
Adrenergic
response
Relaxation
Parasympathetic/
Muscarinic Receptors
a
Cholinergic response
Contraction
Constriction
Constriction
Constriction
d
Constriction
Constriction,
f
dilation
Constriction
Constriction
No innervation
e
No innervation
e
No innervation
Dilation
e
No innervation
No innervation
Responses
Responses
Beta2 ( 2) Receptors
Relax smooth muscle
Adrenergic Effects
1 Heart
stimulation of heart rate
chronotropic effect
stimulation of force of contraction
inotropic effect
Adrenergic Effects
Smooth Muscle Relaxation 2
relaxation of bronchioles 2
relaxation of uterus 2
Skeletal Muscle
2nd Messenger
Receptors
Increased Ca2+
Contract
1, M1, M3, M5
Increased cAMP
Relax
Decreased cAMP
Contract
M2, M4
Decreased cAMP
Relaxation
Note that 1, 2, and 3 receptors INCREASE cAMP, but in smooth muscle 2 receptors
are the predominant type
Note that 1 receptors cause increased heart rate and increased strength of contractionHeart muscle is different than smooth muscle: increased cAMP enhances cardiac function.
Note that muscarinic receptors cause relaxation of sphincters- promote urination and
defecation. Muscarinic receptor mediated release of NO is likely the cause.
Note that 2 receptors cause smooth muscle relaxation. 2 receptors are located presynaptically on norepinephrine (NE) containing neurons. Activation of 2 receptors
reduces NE release. Less NE release means less NE to stimulate smooth muscle of the
blood vessels.
Adrenergic Effects
Metabolic and Hormonal
glycogenolysis 2 (liver)
gluconeogenesis (liver)
lipolysis 3(fat cells)
stimulation of insulin release
stimulation of renin release
Side effects:
muscle tremors, tachycardia (1 and reflex), anxiety,
restlessness, headache, hyperglycemia, hypokalemia
Alpha 1 Agonist
Phenylephrine
1 > 2 activity
Decongestant (oral or spray)
Mydriatic (causes mydriasis)
Increases blood pressure (vasoconstriction)
Alpha 2 Agonist
2 receptors- presynaptic location on
noradrenergic neurons
Decrease the release of NE
Clonidine
2 receptor agonist
Decreases release of NE
Decreases blood pressure, anti-hypertensive
Alpha Blocker
Phentolamine Non-selective competitive
antagonist for alpha-1 and alpha-2 receptors.
Duration of several hours.
Competitive blocker Rapid onset of
blockade. Surmountable by high
concentrations of alpha-1 agonists or alpha-2
agonists.