chapter 381

SYNTHESIS AND SECRETION

AVP is a nonapeptide composed of a six-member disulfide ring and

a tripeptide tail (Fig. 381-1). It is synthesized via a polypeptide precursor

that includes AVP, neurophysin, and copeptin, all encoded by

a single gene on chromosome 20. After preliminary processing and

folding, the precursor is packaged in neurosecretory vesicles, where it

is transported down the axon; further processed to AVP, neurophysin,

and copeptin; and stored in neurosecretory vesicles until released by

exocytosis into peripheral blood.

In healthy individuals, AVP secretion is regulated primarily by the

“effective” osmotic pressure, which is determined largely by the plasma

concentration of sodium and its anions. This regulation is mediated by

specialized cells in the anteromedial hypothalamus, known as osmoreceptors.

The osmoreceptors receive blood from small perforating

branches of the anterior communicating artery. They are extremely

sensitive to small changes in the plasma concentration of sodium and

its anions but normally are insensitive to other naturally occurring

plasma solutes such as urea and glucose. This osmoregulatory system

includes inhibitory as well as stimulatory components that function in

concert to form a threshold, or set point, control system. Below this

threshold, plasma AVP is suppressed to levels that permit the development

of a maximum water diuresis. Above it, plasma AVP rises steeply

in direct proportion to plasma osmolarity, quickly reaching levels sufficient

to produce maximum antidiuresis. The absolute levels of plasma

osmolarity/sodium at which minimally and maximally effective levels

of plasma AVP occur differ from person to person, apparently due to

genetic influences on the set and sensitivity of the system. However,

the average threshold, or set point, for AVP release corresponds to a

plasma osmolarity and sodium of ~275 mosmol/L and 135 meq/L,

respectively; levels only 2–4% higher normally result in maximum

antidiuresis