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:

--> 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

Increased water resorption in kidney
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In absence of ADH, aquaporin is withdrawn from the luminal membrane via endocytosis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

Osmotic stimuli
ECF volume
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