NEURAL CONTROL OF SALIVARY SECRETION

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NEURAL CONTROL OF SALIVARY SECRETION
PARASYMPATHETIC CONTROL SYMPATHETIC
CONTROL EXCITATION SECRETION COUPLING SALIVARY
REFLEXES BUFFERING ACTION OF SALIVA
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Na
100
80
HCO3
60
Concentration (mEq/l)
Cl
40
K
20
0
0
10
20
30
40
Flow of saliva (ml/min)
Classic experiment in which the concentration of
ions in human parotid saliva was measured at
different flow rates produced by parasympathetic
stimulation (Thaysen et al., 1954)
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Afferent (sensory fiber)
Efferent (secretomotor fiber)
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RAT HORIZONTAL BRAINSTEM SECTION
ROSTRAL
CAUDAL
MIDLINE
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CNS
PNS
Target
Sympathetic trunc
1st order neuron
2nd order neuron
Sympathetic nervous system
neurotransmitter
neurotransmitter
Acetylcholine (ACh)
Noradrenalin/ norepinephrin (NA)
2nd order neuron
Parasympathetic nervous system
1st order neuron
neurotransmitter
Acetylcholine (ACh)
neurotransmitter
Acetylcholine (ACh)
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Sympathetic nervous system
Parasympathetic nervous system
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Effect of autonomic nervous system stimulation on
salivary secretion
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Epilemmal
Hypolemmal
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ALL SALIVARY GLANDS ARE INNERVATED BY
PARASYMPATHETIC NERVE FIBERS SYMPATHETIC
INNERVATION IS VARIABLE - NOT ALL GLANDS ARE
INNERVATED AND THE RELATIVE VOLUMES OF SALIVA
PRODUCED BY SYMPATHETIC STIMULATION AND THE TYPES
OF ADRENORECEPTORS ON THE BASOLATERAL MEMBRANE
ARE VARIABLE
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Muscarinergic acetyl cholin receptor mAChR (93
type 3)
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NEUROTRANSMITTERS INVOLVED IN SALIVARY SECRETION
NOREPINEPHRINE binds to either a or b adrenergic
receptors ACETYLCHOLINE binds to muscarinic
cholinergic receptors VASOACTIVE INTESTINAL
PEPTIDE binds to vasoactive intestinal
receptors SUBSTANCE P binds to substance P
receptors
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These neurotransmitters bind to receptors on the
basolateral membrane of the acinar cells. The
receptors belong to a large family of membrane
receptors that transduce their signals via a
guanine neucleotide regulatory protein
(G-protein). Activation of the G-protein results
in the formation of cyclic AMP and eventually
protein exocytosis. Alternatively activation of
the G-protein leads to the formation of IP3,
which leads to Ca2 mobilization and,
subsequently, fluid secretion.
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Na (150)
MEMBRANE POTENTIAL
Cl - (130)
K (3)
K (140)
V -60 to -75 mV
Na (30)
A CELL
Cl - (8)
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BASIC ION CHANNEL
ION CHANNELS ARE PORES THROUGH THE CELL MEMBRANE
THAT ALLOW SELECTIVE PASSAGE OF IONS THROUGH THE
MEMBRANE.
THERE ARE SEVERAL TYPES OF ION CHANNEL
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G-PROTEIN COUPLED ION CHANNEL
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Stimulus-response coupling
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SIGNAL TRANSDUCTION PROCESSES IN SALIVARY GLANDS
1. Generation of cAMP following ?-adrenergic
receptor stimulation, which leads to protein
exocytosis. 2. Formation of 1,4,5-inositol
triphosphate (IP3) after muscarinic acetylcholine
receptor stimulation, which leads to Ca2
mobilization and fluid secretion.
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TIGHT JUNCTION
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7.8
7.6
7.4
7.2
7.0
6.8
Salivary pH
6.6
6.4
6.2
6.0
5.8
5.6
0.0
0.5
1.0
1.5
2.0
Flow rate of parotid saliva (ml/min)
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Different taste qualities induce different flow
rates of saliva
1 M Sucrose
0.05 M Quinine
0.5 M NaCl
0.1 M Tartaric acid
1 M NaCl
0.5 M KCl
0.5 M MgCl2
0.5 M CaCl2
0.5 M NH4Cl
2 M NaCl
0.25 M Tartaric acid
0
2
4
6
8
10
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Flow rate of saliva
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The Nobel Prize in Physiology or Medicine 1986
"for their discoveries of growth factors"
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Neurotrophic Factors are endogenous, soluble
proteins regulating survival, growth,
morphological plastisity, or synthesis of
proteins for different functions in neurons
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Proteins initially characterized as neurotrophic
factors Neurotrophins (NGF, BDNF, NT-3, NT-4,
NT-6) GDNF-family GDNF, NrTN, PSP,
ART CNTF etc.
Proteins not initially characterized as
neurotrophic factors FGF-family aFGF,
bFGF IGF EGF TGF? and ? Interleukin 1, 3, 6 etc.
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Classical
The Neurotrophic Theory

• Neurons are produced in excess during development
• They send out neurites and compete over
  neurotrophic factors in target areas,
• Those that reach target survive

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Families of neurotrophic factors
Neurotrophins
NGF
, BDNF
, NT-3
, NT-4
GDNF family
GDNF
, NTN
, PSP
, ART
Neurokine family
CNTF
, CT-1
, LIF
Transforming growth factor bs
TGFb-1, TGFb-2, TGFb-3
Insulin-like growth factors
IGF-1, IGF-2
Fibroblast growth factors
FGF-1, FGF-2, FGF-5
Hepatocyte growth factor
HGF
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Specificity and promiscuity in the neurotrophin
family
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Specificity and promiscuity in the GDNF family
GFR
-1
a
GDNF
NTN
RET
ART
PSP
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What is a knockout
A. A ballot used in Florida to elect the
president. B. Evander Holyfield losing world
championship title C. A scientists attempt to
use common names for biological experiments
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