review paper by Tania, Beth, Odir, Radu

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• review paper by Tania, Beth, Odir, Radu

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Background Info

• HPA - hypothalamus - pituitary - adrenocortical
  axis
• i.p. injection - intraperitoneal injection (intra
  serous membrane lining the abdominal cavity and
  its organs)
• cytokines - soluble long chains of amino acids
  secreated by cells of the immune system
• interleukin - cytokines secreated by leukocytes
  in response to body inflamatory response.
• nitric oxide - unstable gas produced in brain
  tissue involved in HPA control - very short
  half-life
• nicotine - a stimulant and inhibitory substance
  capable of crossing BrainBloodBarrier acting on
  nicotinic acetylcholine receptors and increasing
  Dopamine levels (reward circuit)

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Experimental Design

• the effects of NO in the Interleukin and
  Nicotine-induced HPA axis response under social
  pressure conditions
• the effects of CRH and (vasopressin)
  AVP-antagonists in the nicotine-induced HPA axis
  stimulation under social pressure conditions

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INTERLEUKIN induced HPA ACTH
CorticosteronePURPOSE

• It was investigated the role of L-NAME on the
  interleukin induced (IL-1beta) HPA stimulation.
  (HPA hypothalamic-pituitary-adrenal axis)
• L-NAME is a NO non-selective inhibitor.

Effects of NO
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INTERLEUKIN induced HPA ACTH
CorticosteroneDRUGS used

• Interleukin 1beta mouse recombinant, expressed in
  E-coli (interleukin extracted from mouse,
  clonned with E-coli).
• L-NAME (N-omega-nitro-L-arginine methyl ester
  HCL) inhibitor of NOS (NOS - nitric oxide
  synthase is a catalyst).

Effects of NO
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INTERLEUKIN induced HPA ACTH
CorticosteronePROCEDURE

• injected L-NAME
• they induced HPA stimulation with interleukin
• waited 1 hour for the effects to occur
• collected blood samples
• measured and compared results between Basal and
  Stress subjects

Effects of NO
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INTERLEUKIN induced HPA ACTH
CorticosteroneFINDINGS

• Interleukin alone stimulated HPA by producing
  large quantities of ACTH / Corticosterone
• L-NAME (a non-selective inhibitor) partly blocked
  Interleukin HPA stimulation, which produced less
  quantities of ACTH / Corticosterone
• When comparing Basal versus Stress stimulants,
  the Stress subjects had an overall LESS
  stimulation of HPA with a decrease in ACTH /
  Corticosterone production

Effects of NO
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INTERLEUKIN induced HPA ACTH
CorticosteroneCONCLUSION

• Stress subjects had a decrease in the ACTH/
  Corticosterone response to Interleukin stimulus
• Since L-NAME had positive effects on the
  ACTH/Corticosterone serum levels induced by
  Interleukin, Nitric Oxide played a major role in
  HPA response to Interleukin administration
• (L-NAME is a Nitric Oxide non-selective inhibitor)

Effects of NO
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NICOTINE induced HPA ACTH CorticosteronePURPOS
E

• It was investigated the effects of (eNOS),
  (nNOS), and (iNOS) antagonists on the nicotine
  induced HPA axis.
• eNOS endothelial nitric oxide synthasenNOS
  neuronal nitric oxide synthaseiNOS inducible
  nitric oxide synthase (inflammatory response)
• NO blockade generated by NO synthase antagonists
  affects ACTH and Corticosterone response to
  cholinergic agonists and neuropeptides.

Effects of NO
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NICOTINE induced HPA ACTH CorticosteroneDRUGS
used

• L-NAME - inhibitor of eNOS (antagonist)
• L-NNA - inhibitor of nNOS (antagonist)
• AG Aminoguanide - inhibitor of iNOS (antagonist)

Effects of NO
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NICOTINE induced HPA ACTH CorticosteronePROCED
URE

• injected L-NAME, L-NNA, AG
• they induced HPA stimulation with Nicotine
• waited 1 hour for the effects to occur
• collected blood samples
• measured and compared results between Basal and
  Stress subjects

Effects of NO
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NICOTINE induced HPA ACTH FINDINGS

• Basal There was no inhibition of the ACTH
  serum level by the L-Name, L-NNA, and AG on the
  Nicotine induced HPA stimulation (with the
  Nicotine stimulation)
• Stress Overall, the ACTH production was
  inhibited when administered NOS antagonists and
  the Nicotine.The greatest inhibition was by
  L-NAME (eNOS antagonist)L-NNA had no influence
  on the ACTH production induced by NicotineAG had
  no influence on the ACTH production induced by
  Nicotine

Effects of NO
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NICOTINE induced HPA ACTH CONCLUSION

• Stress greatly inhibited the ACTH production by
  the NOS antagonists and Nicotine
• L-NAME produced the greatest inhibition of ACTH
  Nicotine induced HPA production
• This meant that eNOS played a major role in HPA
  axis control under stressful conditions

Effects of NO
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NICOTINE induced HPA CORTICOSTERONEFINDINGS

• Basal There was no inhibition of the
  Corticosterone serum level by the L-Name, L-NNA,
  and AG on the Nicotine induced HPA stimulation
  (with the Nicotine stimulation)
• Stress Overall, the Corticosterone production
  was inhibited when administered NOS antagonists
  and the Nicotine.The greatest inhibition was by
  L-NAME (eNOS antagonist)L-NNA had no influence
  on the Corticosterone production induced by
  NicotineAG had no influence on the
  Corticosterone production induced by Nicotine

Effects of NO
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NICOTINE induced HPA CORTICOSTERONECONCLUSION

• Stress greatly inhibited the Corticosterone
  production by the NOS antagonists and Nicotine
• L-NAME produced the greatest inhibition of
  Corticosterone Nicotine induced HPA production
• This meant that eNOS played a major role in HPA
  axis control under stressful conditions

Effects of NO
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NICOTINE induced HPA ACTH CorticosteronePURPOS
E

• It was investigated the effects of CRH and AVP
  antagonist on nicotine induced ACTH/corticosterone
  secretion (due to HPA stimulation) in both
  stressed and non-stressed rats.

Effects of CRH AVP
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NICOTINE induced HPA ACTH CorticosteroneDRUGS
used

• Corticotropin Releasing Factor antagonist - Anti
  CRH
• Vasopressin Receptor antagonist - Anti AVP

Effects of CRH AVP
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NICOTINE induced HPA ACTH CorticosteronePROCED
URE

• injected with Anti-CRH and Anti AVP
• induced HPA with Nicotine
• waited 1 hour for the effects to occur
• collected blood samples
• measured and compared results

Effects of CRH AVP
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NICOTINE induced HPA ACTH CorticosteroneFINDIN
GS

• Nicotine alone stimulated HPA by producing large
  quantities of ACTH / Corticosterone
• Anti-CRH produced partial inhibition of the ACTH
  / Corticosterones stimulation by Nicotine induced
  HPA
• Anti AVP had variable results- large reduction
  of the ACTH stimulation- no effect on the
  Corticosterone stimulation

Effects of CRH AVP
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NICOTINE induced HPA ACTH Corticosterone CONCLU
SION

• CRH plays a major role in HPA stimulation
• There are ambiguous results concerning AVP's role
  in HPA stimulation
• It can be concluded that Vasopressins play a role
  in the ACTH but not in the Corticosterone
  production

Effects of CRH AVP
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Integrated Conclusion
interleukin induced HPA (ACTH /
Corticosterone)Stress subjects had a decrease in
the ACTH/ Corticosterone response to Interleukin
stimulus. nicotine induced ACTHStress greatly
inhibited the ACTH production by the NOS
antagonists and Nicotine. nicotine induced
CorticosteroneStress greatly inhibited the
Corticosterone production by the NOS antagonists
and Nicotine. nicotine induced HPA in both Bassal
and Stressed subjectsCRH plays a major role in
HPA stimulationThere are ambiguous results
concerning AVP's role in HPA stimulationIt can
be concluded that Vasopressins play a role in the
ACTH but not in the Corticosterone production
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• review paper by Tania, Beth, Odir, Radu