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NEURAL CONTROL OF SALIVARY SECRETION

NEURAL CONTROL OF SALIVARY SECRETION. PARASYMPATHETIC CONTROL SYMPATHETIC CONTROL EXCITATION SECRETION COUPLING SALIVARY REFLEXES BUFFERING ACTION OF SALIVA. Na. 100. 80. HCO 3. 60. Concentration (mEq/l). Cl. 40. K. 20. 0. 0. 10. 20. 30. 40. Flow of saliva (ml/min).

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NEURAL CONTROL OF SALIVARY SECRETION

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  1. NEURAL CONTROL OF SALIVARY SECRETION PARASYMPATHETIC CONTROL SYMPATHETIC CONTROL EXCITATION SECRETION COUPLING SALIVARY REFLEXES BUFFERING ACTION OF SALIVA

  2. 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)

  3. PNS CNS Label HRP Afferent (sensory fiber) Efferent (secretomotor fiber)

  4. TERMINATION OF GLOSSOPHARYNGEAL NERVE FIBERS CELL BODIES OF INFERIOR SALIVATORY NUCLEUS RAT HORIZONTAL BRAINSTEM SECTION ROSTRAL CAUDAL MIDLINE

  5. CNS PNS Target Sympathetic trunc 1st order neuron 2nd order neuron Sympathetic nervous system neurotransmitter Acetylcholine (ACh) neurotransmitter Noradrenalin/ norepinephrin (NA) 2nd order neuron Parasympathetic nervous system 1st order neuron neurotransmitter Acetylcholine (ACh) neurotransmitter Acetylcholine (ACh)

  6. Sympatheticnervous system Parasympatheticnervous system

  7. Effect of autonomic nervous system stimulation on salivary secretion

  8. Epilemmal Hypolemmal

  9. 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

  10. Muscarinergic acetyl cholin receptor mAChR (93% type 3)

  11. 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

  12. 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.

  13. NEUROTRANSMITTER ADENYLATE CYCLASE G PROTEIN MEMBRANE RECEPTOR Stimulus-response coupling

  14. APICAL BASOLATERAL TIGHT JUNCTION

  15. 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)

  16. 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 12 Flow rate of saliva

  17. Rita Levi-Montalcini Italy and USA Institute of Cell Biology of the C.N.R. Rome, Italy Stanley Cohen USA Vanderbilt University School of Medicine Nashville, TN, USA The Nobel Prize in Physiology or Medicine 1986 "for their discoveries of growth factors"

  18. Neurotrophic Factorsare endogenous, soluble proteins regulating survival, growth, morphological plastisity, or synthesis of proteins for different functions in neurons

  19. 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.

  20. 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

  21. The neurotrophic hypothesis

  22. Predictions of the neurotrophic hypothesis Target ablation / null mutation Increased target / overexpression

  23. Biological activities of neurotrophic factors control GDNF differentiation no factor GDNF neuron survival Kang & Schuman (1995) Science 26, 1658-1662 no factor NGF synaptic plasticity neurite outgrowth

  24. Families of neurotrophic factors , NT-4 , NT-3 Neurotrophins NGF , BDNF GDNF family GDNF , NTN , PSP , ART , LIF , CT-1 Neurokine family CNTF 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

  25. TrkA NGF BDNF TrkB NTR p75 NT-3 TrkC NT-4 Specificity and promiscuity in the neurotrophin family

  26. GFR -2 a GFR -3 a GFR -4 a Specificity and promiscuity in the GDNF family GFR -1 a GDNF NTN RET ART PSP

  27. What is a knockout A. A ballot used in Florida to elect the president. B. Evander Holyfield losing world championship title C. A scientist’s attempt to use common names for biological experiments

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