Potency
Partial agonists
give a partial effect, even at saturating concentrations.
Neutral agonists
Does nothing to the activity of the target even though it binds
Inverse agonists
Suppress the basal level of signaling of a biomolecule.
The autonomic nervous system is activated mainly by centers located in the. . .
spinal cord, brain stem, and hypothalamus.
Portions of the cerebral cortex may also send signals down to these three regions to regulate their activity.
Characteristics of sympathetic activation
- Activation of the reticular system (alertness)
- Feeling of energy and euphoria and ignorance of pain (endorphin release)
- Increased heart rate, breathing rate, deepness of breath (mediated by pons and medulla oblongata)
- Elevation of muscle tone
- Activation of sweat glands
- Mobilization of glycogen and triglyceride energy stores (glucagon secretion)
Characteristics of parasympathetic activation
- Constriction of the pupils
- Secretion by digestive glands
- Secretion of insulin and anabolism
- Changes in blood flow associated with sexual arousal
- Increased gut peristalsis
- Loosening of rectal and internal urinary sphinctres
- Constriction of respiratory passages
- Reduction in heart rate and contraction force
Origin of a somatic motor signal
Origin of an autonomic motor signal
Sympathetic motor neurons synapse in ____. Parasympathetic motor neurons synapse in ____.
Sympathetic motor neurons synapse in sympathetic chain ganglia. Parasympathetic motor neurons synapse in ganglia in the vicinity of the tissues they innervate.
In the somatic motor system, muscle relies on innervation for ____.
In the autonomic motor system, muscle relies on innervation for ____.
In the somatic motor system, muscle relies on innervation for all activity.
In the autonomic motor system, muscle relies on innervation for tuning activity up or down.
The one exception to the sympathetic = adrenergic rule
Sweat glands are innervated by sympathetic cholinergic neurons and utilize the muscarinic receptor.
Thoracolumbar system
Aka the sympathetic chain, associated ganglia, and innervated organs
So named because it arises in T1 and goes until L2/L3.
Craniosacral system
Aka the parasympathetics of the brain stem (CN III, VII, IX, X) and sacral vertebrae, associated ganglia, and innervated organs.
Cranial nerve X
Better known as the vagus nerve.
Provides parasympathetic innervation to the major organs in the chest and abdomen, including the heart, tracheobronchial tree, kidneys, and GI system down to the proximal colon.
Parasympathetic nerves originating in the sacral region of the spinal cord innervate the remainder of the colon, urinary bladder, and genitalia.
Catecholamine biosynthesis pathway
Adrenergic neuron diagram
Cocaine
Norepinephrine transporter blocker
Prevents norepinephrine reuptake
Reserpine
Blocks re-loading of catecholaminergic granules in adrenergic neurons via the VMAT (Vesicular monoamine transporter) channel.
This prevents only re-loading of granules, reuptake is not affected.
α1 receptors
Expressed in:
Smooth muscle, heart, liver
Effects:
Contraction of vacsular and genitourinary smooth muscle, relaxation of intestinal smooth muscle. Increased cardiac inotropy (contraction force), glycogenolysis and gluconeogenesis in liver.
Mediators:
Gq/Gi/Go
β1 receptors
Expressed in:
Heart, renal juxtaglomerular cells
Effects:
Tachycardia, increased cardiac inotropy, increased atrioventricular node conduction velocity, renin secretion in juxtaglomerular cells.
Mediators:
Gs
α2 receptors
Expressed in:
Pancreatic β cells, platelets, nerves, vascular smooth muscle
Effects:
Decreased insulin secretion, aggregation of platelets, decreased norepinephrine release in adrenergic neurons, contraction of vascular smooth muscle
Mediators:
Gi/Go
β2 receptors
Expressed in:
Smooth muscle, liver, skeletal muscle
Effects:
Smooth muscle relaxation, glycogenolysis and gluconeogenesis in liver, glyogenolysis and K+ uptake in skeletal muscle.
Mediators:
Gs
β3 receptors
Expressed in:
Adipose tissue
Effects:
Lipolysis
Mediators:
Gs
Adrenergic receptor agonists
Calcium-induced calcium release
Systole is mediated by ____, while diastole is mediated by ____.
Systole is mediated by rapid rise in cardiac myocyte calcium levels, while diastole is mediated by ATP-dependent calcium pumps which remove calcium from cardiac myocytes.
Phospholamban
Binds to and inhibits the SERCA pump in cardiac myocytes.
Part of the system that regulates the tuning of cardiac contractions by the autonomic nervous system.
Activation of β1 cardiac receptors in cardiac myoctes leads to. . .
Activation of adenylyl cyclase and Protein Kinase A (PKA). Downstream, this causes phosphorylation of L-type calcium channels, NCX channels, RyR2 receptors, and phospholamban.
The phosphorylation of these proteins leads to a higher level of calcium in the cytoplasm, which causes a greater degree of contraction during systole.
The phosphorylation of phospholamban blocks its ability to inhibit SERCA, allowing SERCA to move calcium faster and counterbalancing the greater systolic pressure with a greater diastolic pressure.
Sympathetic stimulation induces ___ in the GI tract.
Sympathetic stimulation induces muscle relaxation in the GI tract.
Where does muscle relaxation require ATP?
Powering the Calcium ATPase to pump calcium back outside of the cell or into the SR.
ATP is sequestered by the tropomyosin relaxation, but is not consumed.