Antidiuretic hormone (aka Vasopressin)

[Ref: WG22:p242-247]

Both ADH and oxytocin has 9 amino acid residues

Production and release

• ADH and oxytocin are both synthesized in the cell bodies of the magnocellular neurons in the supraoptic and paraventricular nuclei (in anterior hypothalamus)
• Both are transported down the axon by axoplasmic flow
  --> Released at the posterior pituitary
• Some cells produce vasopressin and some produce oxytocin
• Both types found in both nuclei
• Secretory granule in the nerve is called Herring bodies
• Precursors are processed (cleaved) in the granule during transport
• Action potential from the cell bodies down the axon leads to release of hormone
  * via Ca2+ dependent exocytosis

Vasopressin receptors

At least 3 types:

• V1A
• V1B
• V2

--> All G protein-coupled

V1A and V1B receptors

• Both act via phosphatidylinositol hydrolysis
  --> Increase intracellular Ca2+
• Mediate vasoconstriction in blood vessels

V2 receptor

• Act via Gs protein
  --> Increase cAMP
• Coded on the X chromosome
• In the basolateral membrane of the principle cells

Effects of ADH

2 main effects

1. Increased water resorption in kidney
2. Vasoconstriction

Other minor effects

• Glycogenolysis in liver (via V1A receptors)
• A neurotransmitter in brain and spinal cord
  * Significance unsettle
• [AV6:p119] ADH also increase sodium resorption by cortical collecting ducts (synergic action with aldosterone in the same segment)

1. Antidiuretic effect

via V2 receptors
--> Activate adenylate cyclase
--> Increase cAMP
--> Insertion of aquaporin 2 into the luminal membrane of the principle cells in the collecting ducts (by fusion of intracellular vesicles)

• Increased water resorption
  --> Decreased urine output
  --> Water retention and decrease plasma osmolarity
• Can be so significant that increase in ECF stimulate aldosterone (via angiotensin II) and cause even greater hyponatremia

NB:

• Maximal antidiuretic effect is achieved at lower concentration of ADH than that required to produce vasoconstriction effect
• In absence of ADH, aquaporin is withdrawn from the luminal membrane via endocytosis

2. Vasoconstrictor effection

via V1A receptors

However, because vasopressin also causes decrease in cardiac output
* By acting on area postrema in brain

Thus,
* Large quantities of vasopressin is needed to increase BP

 

Metabolism of ADH

• Rapidly inactivated
• Inactivated in liver and kidney
• Halflife: 18 minutes
• Effects on kidney: rapid onset, but short duration

 

Control of ADH secretion

1. Osmotic stimuli
2. ECF volume
3. Others

1. Osmotic stimuli

Increase in osmotic pressure of the plasma

--> Detected by osmoreceptors in the anterior hypothalamus
* Probably organum vasculosum of lamina terminalis (OVLT)

--> Increased ADH secretion

NB:

• ???? the same osmoreceptors that mediate thirst as well
• Response threshold is 1 to 2% change in osmolarity
  * [KB2:p23]

 

2. ECF volume

Decrease in ECF volume

--> Detected by baroreceptors and volume receptors
* Volume receptors are the primary detector
* Response threshold for volume receptor is 7 to 10% change in volume [KB2:p23]

--> Signals via vagi to the nucleus of tractus solitarius (NTS)

--> Inhibitory pathway from NTS to caudal ventrolateral medulla (CVLM)

--> Excitatory pathway from CVLM to hypothalamus

NB:

• Decreased ECF volume also stimulate angiotensin II release, which also increase ADH secretion
• At small to low

Osmoreceptor vs volume receptor

Osmoreceptor is quite sensitive
--> At small to moderate volume loss, osmoreceptor overrides volume receptors in controlling ADH

But at high volume loss, volume receptor overrides osmoreceptor in controlling ADH

NB:

• Volume stimuli tend to be less sensitive but more potent than osmotic stimuli
  * [KB2:p23]

3. Other factors

Stimulate vasopressin secretion

Nausea causes large increases in vasopressin secretion

Other factors that increase secretion:
* Pain, stress, exercise, emotion
* Standing
* Angiotensin II

Inhibits vasopressin secretion

Alcohol decrease vasopressin secretion

Synthetic agonist

Desmopressin (DDAVP)

• Very high antidiuretic activity
• Very little pressor activity