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CASE FILES: BIOCHEMISTRY
the condition may result from mutations in the vasopressin receptor or aqua-
porin genes or other diseases impairing renal response to vasopressin. When
injected in pharmacologic doses, vasopressin acts as a vasoconstrictor.
There are two major types of vasopressin receptors, V1 and V2. The V1
receptor occurs in vascular smooth muscle and is coupled via Gq to activation
of the phosphoinositide cascade-signaling system and generation of the second
messenger inositol trisphosphate (IP3) and diacylglycerol. V2 receptors are
found in kidney and are coupled via Gs to activation of adenylate cyclase and
production of the second messenger cyclic AMP.
The steroid hormone aldosterone, synthesized in the zona glomerulosa of
the adrenal cortex, also plays an important role in maintaining blood osmolar-
ity. It binds its receptors in the cytoplasm of epithelial cells of the distal colon
and the renal nephron, followed by translocation of the hormone-receptor
complex to the nucleus and activation of transcription of ion transport genes to
increase Na+ reabsorption and K+ secretion. Water follows Na+ movement by
osmosis. These transporters include the luminal amiloride-sensitive epithelial
Na+ channel, the luminal K+ channel, the serosal Na+, K+-ATPase, the
Na+/H+exchanger, and the Na+/Cl- cotransporter.
Vasopressin and aldosterone each act on the kidney to increase fluid reten-
tion and both are in turn regulated by angiotensin II. Renin is a proteolytic
enzyme that is released from the kidney in response to sympathetic neuron
stimulation, renal artery hypotension, or decreased Na+ delivery to renal distal
tubules. Renin cleaves circulating angiotensinogen to form the decapeptide
angiotensin I. Then angiotensin converting enzyme (ACE) found primarily in
lung removes two amino acids from angiotensin I to form the octapeptide
angiotensin II. In addition to other important targets in regulating blood vol-
ume, arterial pressure and cardiac and vascular function, angiotensin II stimu-
lates aldosterone release from the adrenal cortex and vasopressin release from
the posterior pituitary. The actions of angiotensin II are mediated by plasma
membrane seven-helix receptors coupled via Gq signaling by the phospho-
inositide pathway.
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