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● Nitric oxide = potent vasodilator

Feature Autocrine or Nervous Endocrine Exocrine ○ Induce cGMP = vasodilation


Paracrine ○ Can easily be cleared by body by phosphodiesterase = stop vasodilation
○ Viagra = phosphodiesterase inhibitor = more cGMP = prolonged vasodilation =
Secretory Various Neural Endocrine Various erection
Cell Purines
● Neuromodulators & paracrines
Target Cell Most cells in Neuron, Most cells in Sensory and ● Adenosine, AMP, ATP, GTP
body muscle, body neural
endocrine
Receptor isoforms
● Epinephrine (expressed on diff target cells)
Signal Type Chemical Electrical and Chemical Chemical ○ Lungs = vasodilation
chemical
○ Heart = vasoconstriction

Maximum Short Long Long Very long Law of Mass Action


Signaling intracellularly,
● Free L or R = increase response
Distance short across
synapse ● R Saturated at high L = maximal response

Transport Extracellular Synapse Circulatory External Down Regulation


fluid system environment ● Decrease # of R due to high L
● Opiate drugs (heroin) -> addiction
Speed Rapid Rapid Slower Various ○ Causes brain to be relaxed when it shouldnt be
○ Body will downregulate and hide receptors from cell wall
○ Drug will cause less effect even if intake is same = consume more for the
Duration of Short Short Longer Various
Response effect
Up Regulation
● Increase number of R
● Caffeine (attaches to adenosine)
Features Hydrophilic Hydrophobic ○ Adenosine induce relaxation (dec brain act)
Messengers Messengers ○ Caffeine attaches to adenosine so brain wont relax
○ Receptor blocked = brain signal rest = produce more target cells so adenosine
Storage Intracellular vesicles Synthesized on demand would bind more to receptor
○ Body will be dependent on caffeine cos more receptors are produced n
Secretion Exocytosis Diffusion across membrane bonded w adenosine = brain to relax
○ More receptors = normal caffeine = make ur body sleepy
Transport Dissolved in extracellular Short distances: L-R dynamics
fluids Dissolved in extracellular ● Higher affinity constant (Ka) -> higher response
fluid ● Ka is 50% of R occupied
● High affinity R = lower Ka
Long distances:
● Low affinity R = higher Ka (take longer to reach 50% of R)
Bound to carrier proteins

Receptor enzymes
Receptor Transmembrane Intracellular or
● Guanylate cyclase
transmembrane
○ GTP -> cGMP -> activate PKG or CGMP dependent kinase
○ Atrial natriuretic peptide (ANP) : increase blood pressure = stretching = dec bv
Effects Rapid Slower or rapid
● Tyrosine Kinase
Peptide Hormones (hydrophilic) ○ Phosphorylation of tyrosine (autophosphorylation)
● Rough ER ○ Ras proteins: mutation; phosphorylates = inc production of substances =
● Preprohormones -> cleavage -> prohormone (vesicle) -> enzyme breakdown -> overamplification
active form ● Serine/Threonine Kinase
● Arginine-Vasopressin (fluid balance) ○ Direct phosphorylation of serine/threonine
○ Preprovasopressin (SP + AVP + neurophysin + glycoprotein) ○ TGF beta = like ras where overamplification
○ SP cleaved in RER = provasopressin
○ Cleavage in GA = AVP, NPH, GP
Steroid hormones (hydrophobic) Second Synthesized Action Effects
Messengers by the
● Synthesized in Smooth ER or mitochondria enzyme
● 3 classes: Mineralocorticoids, Glucocorticoids, Reproductive Hormones
● Cholesterol + desmolase -> pregnenolone -> progesterone
Ca2+ None Binds to Alters enzyme
○ 17-alpha hydroxylase = cortisol & sex hormone (testosterone, estrogen) calmodulin activity
○ 21-hydroxylase = aldosterone (sodium goes, water goes)
Amine Hormones
cGMP Guanylate Activates Phosphorylates
● Hydrophilic except thyroid hormones cyclase protein kinases proteins
● ACh, catecholamines (dopamine, nore, epinephrine), serotonin, melatonin, (usually protein
histamine, thyroid hormones kinase G) Opens and closes
● Cytokines are synthesized on demand ion channels
● Tyrosine (thyroid & catecholamines)
● Tryptophan (serotonin & melatonin) cAMP Adenylate Activates Phosphorylates
● Histidine (histamine) cyclase protein kinases proteins
Eicosanoids (hydrophobic) (usually protein
kinase A) Opens and closes
● Act as paracrines
ion channels
● Inflammation & pain: leukotrienes & prostaglandins
● Arachidonic acid (20C)
Phosphatidyl Phospholipase Activates Alters enzyme
○ COX (cyclooxygenase)
inositol C protein kinases activity
■ Prostaglandins, prostacyclines, thromboxanes C
■ Pain Phosphorylates
■ Celecoxib- inhibits COX = no pain Stimulates proteins
○ LOX (lipooxygenase) Ca2+ release
■ Leukotrienes from
intracellular
■ Inflammation
stores
● NSAIDS: ibuprofen, paracetamol, naproxen; inhibit COX/LOX

Gases Feedback regulation


● Act as paracrines (NO, CO) ● Direct feedback loop
○ Directly send signals to endocrine gland w/o going to brain
○ ANP, glucagon & insulun Glycine glycine ionotropic CNS inhibitory
● First order
○ Hypothalamus = integrating center; receives sensory input aspartate aspartate Ionotropic CNS Excitatory
○ Oxytocin and vasopressin
● 2nd order glutamate AMPA ionotropic CNS Excitatory
○ Prolactin
○ Release prh = anterior pituitary to produce prl NMDA ionotropic CNS excitatory
● 3rd order
○ Other anterior pituitary hormones
○ PIH/dopamine, TRH (thyrotropin), CRH (corticotropin), GnRH (gonadotrophic),
mGlu1-8 metabotropi CNS Excitatory or
GHRH (growth)
c inhibitory
Pituitary hormones
● Anterior (adeno) GABA GABA-A ionotropic CNS Inhibitory
○ Hypothalamus -> hypothalamic-pituitary portal system -> ant pituitary
○ Tropic hormones (cause release of another hormone) GABA-B metabotropi CNS Generally
○ 3rd order except prolactin c inhibitory
● Posterior (neuro); extension of hypothalamus
○ Oxytocin & vasopressin; neurohormones Biogenic amines
● Hormones produced by hypothalamus are stored in posterior pituitary
Dopamine Dopamine metabotropi CNS Excitatory or
Arthropods
c inhibitory
● Crustacean hyperglycemic hormone (CHH)
● Low glucose ; neurohormone crab eyestalk
● Low glucose -> close of K ion channels = interior more positive
Norepinephr α and β metabotropi CNS and Excitatory or
● Depolarization = release of CHH that binds to receptors on target cell to produce
ine adrenergic c peripheral inhibitory
glucose
nervous
system
(PNS),
K, Po4, Mg, SO4, fats, proteins Na, Cl, Ca, HCO3, glucose cardiac
muscle,
● K = attract (-)
smooth
● Na = repel (+)
muscle
● Cl = repel (-)

Epinephrine α and β metabotropi Cardiac Excitatory or


adrenergic c muscle, inhibitory
Electrical synapse Chemical synapse smooth
muscle,
Rare in complex animals Common in complex animals CNS

Common in simple animals Rare in simple animals


Peptides
Fast Slow
Endorphins opiate metabotropi CNS Generally
c inhibitory
Bi-directional Unidirectional

Neuropeptid NPY metabotropi CNS Excitatory or


Postsynaptical signal is similar to Postsynaptic signal can be different
presynaptic eY c inhibitory

Excitatory Excitatory or inhibitory Other


Regulating signal
Adenosine purine metabotropi CNS Generally
1. Acetyl CoA is synthesize in the mitochondria
c inhibitory
2. Choline acetyl transferase catalyzes the conversion of choline and acetyl CoA
to acetylcholine (ACh)
3. The ACh is packaged into synaptic vesicles Nitric oxide none N/A N/A N/A
4. ACh is release into the synapse
5. ACh binds to its receptor on the postsynaptic cell
6. Acetylcholinesterase (AChE) breaks down ACh into choline and acetate,
terminating the signal in the postsynaptic cell
7. The presynaptic cell takes up and recycle the choline, and the acetate diffuses
out of the synapse

Neurotrans Receptor Receptor Receptor Effect


mitter type location

Acetylcholin nicotinic ionotropic Skeletal Excitatory


e muscles,
autonomic
neurons,
CNS

Musarinic metabotropi Smooth and Excitatory or


c cardiac inhibitory
muscle,
endocrine
and
exocrine
glands, CNS

Amino acids
Cholinergic Receptors (acetylcholine) Summary: Phases of Action Potential
Receptor Location Effect of 2nd Agonists Antagoni AP Phase Na+ Na+ K+ K+ Membrane
subtype binding messeng sts Channel flow Channel Flow Potential
er
pathway Depolarization open Influx closed none – to -
(ecf ->
Nicotinic Neuromu Excitation Ion influx ACh, Curare icf)
(synapse scular nicotine,
s) junctions, carbachol Overshoot (peak open influx closed none 0 to +
ganglioni of action
c potential)
neurons,
adrenal
Repolarization closed none open efflux + to -
medulla
Hyperpolarization closed none open efflux - to –
Muscarini Gut Excitation G-protein Ach, Atropine,
c coupled muscarin scopolam
e, ine
carbachol Summary: Refractory Period

Absolute Refractory Relative Refractory


Heart Inhibition Period period

Bronchiol Excitation Phase of action potential Depolarization to hyperpolarization


es (lung) repolarization

Sweat Activation Sodium channel gates Closed activation and Closed inactivation
glands inactivation gates gate or resting

Blood Inhibition Production of 2nd action impossible Possible with


vessels potential suprathreshold
of stimulus
skeletal
muscle
Adrenergic (all are metabotropic)
Summary: Graded and Action Potentials

Receptor Location (in Effect (in 2nd Sensitivity Graded potential Action Potential
subtype humans) humans) messenger
system Location of event Dendrites and cell Axon hillock
body
α1 Blood Vasoconstric G protein NE > E
vessels of tion activates Distance Traveled short Long distance - all
skin, gut, phospholipa throughout the length
kidneys, se C of axon
salivary
glands Amplitude Various (graded) and Constant (100 mV)
decremental
Α2 Membrane Inhibits G protein NE > E
(inhibitory) of release of inactivates Stimulus for opening of Chemical Voltage regulated
adrenergic NE adenylate ion channels (neurotransmitter) or
axon cyclase, sensory stimulus
terminals inhibits
cAMP Positive feedback cycle absent present
production (propagation)

β1 Heart Increases G protein NE = E Repolarization Voltage independent Voltage dependent; K


heart rate activates channels open; Na
and strength adenylate channels close
cyclase,
activates
Summation Possible (temporal or Does not occur; all or
cAMP
spatial) none phenomenon
production

β2 Lungs Dilates G protein E > NE NEUROMUSCULAR JUNCTION NOTES:


bronchial activates A Band - Myosin and SOME Actin
passages adenylate I Band - ACTIN ONLY -> stabilized by nebulin
cyclase, H Band - Myosin ONLY - >stabilized by titin
activates
cAMP Microtubule
production ● Alpha = nega
● Beta = posi; growth occurs here
● MTOC = nega; empty dynein moves here
● membrane/integral proteins = posi; kinesin moves here
Actin
● G polymers -> Faction
● Sponty growth (+ end)
● Membrane attachment = dystrophin
● Actin bundles = fascin
● Actin network = filamin
● Filapodia (rodlike) = neural connection; microvili
● Lamellapodia (sheetlike) = leukocytes, macrophages
characteristic Sympathetic Parasympathetic (medulla
(hypothalamus) FIGHT oblongata) REST &
OR FLIGHT DIGEST

Number of neurons in 2 2
chain

Location of cell bodies Thoracic & lumbar regions Hindbrain; sacral region of
of spinal cord spinal cord

Location of ganglia Close to spinal cord Close to effector organ

Preganglionic neuron short long

Postganglionic neuron long short

Synapses per Many few


preganglionic neuron

Neurotransmitter released ACh ACh


by preganglionic neuron

Neurotransmitter released NE ACh


by postganglionic neuron

olfactory Sense of smell sensory telen

optic vision sensory dien

occulomotor Move and blink motor mid


eyes Frontal - reasoning, planning, some speech aspects
Parietal - movement, orientation, recognition, stimuli perception
trochlear Move eyes motor mid Temporal - perception and recognition of auditory stimuli, memory, speech
Occipital - visual processing
trigeminal Face sensation, mixed pons
⅔ tongue

abducens Ability to move motor pons


eyes

facial Facial mixed pons


expression, ⅓
taste

vestibulocochlear Hearing and sensory medulla


balance

glossopharyngeal Taste and mixed medulla


swallow

vagus Digestion and mixed medulla


heart rate

accessory Shoulder and motor medulla


neck

hypoglossal Move tongue motor medulla

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