Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

III. Neurohypophysis
587
Arginine vasopressin (AVP) Cys.Tyr.Phe.Gln.Asn.Cys.Pro.Arg.Gly–NH 2
Lysine vasopressin (LVP) - - - - - - - Lys -
Arginine vasotocin (AVT) - - Ile - - - - - -
Conopressin S (snail venom) - Phe.Ile.Arg - - - - -
Mesotocin (MT) - - Ile - - - - Ile -
Oxytocin (OT) - - Ile - - - - Leu -
* * * * *
FIGURE 18-14 Sequence comparison of
vasopressin (VP) and oxytocin (OT)-like peptides.
Lines between shaded boxes represent
intrachain disulfide bridges. See the legend for
Figure 18-6 .
hypothalamic neurons produces only one hormone, either
VP or OT. The VP and OT genes are located within the
same chromosomal locus at a very short distance from each
other in a head-to-head orientation organization ( Burbach
et al. , 2001 ). Regulatory domains in this intergenic region
control their hypothalamus-specific expression ( Fields et al. ,
2003 ).
The VP gene consists of three exons that encode for
different functional parts of the VP precursor peptide, the
propressophysin. Exon 1 encodes the signal peptide, the
nonapeptide VP, and the N-terminal part of neurophysin II
(NP-II). Exon 2 encodes the central part of NP-II, and exon
3 encodes the C-terminal part of NP-II and a glycoprotein
(GP). The major factors that regulate VP expression are
osmotic and hypovolemic stimuli. Water deprivation stimulates
hypothalamic VP mRNA most probably through two
cAMP response elements (CRE) and an AP2 site within
the promoter. Glucocorticoids suppress VP gene expression
through a GRE in the VP promoter ( Kim et al. , 2001 ).
2 . (Pro)hormone
After cleavage of the signal peptide, the GP moiety of the
VP prohormone is glycosylated, disulfide bonds are generated,
and then the prohormone is packaged into a secretory
vesicle. The correct sorting of the prohormone into the
secretory pathway requires the formation of aggregates.
Specific association of VP and NP-II results in dimeric and
tetrameric units that are essential for sorting ( Burbach et
al. , 2001 ). The secretory vesicles are axonally transported
to the axon endings in the posterior pituitary. Studies in
the dog suggest that approximately 1.5 h are required from
the time of synthesis to possible release of the nonapeptide
( Ivell et al. , 1986 ). During this transport the neurophysin
II, VP, and the GP moiety are liberated by proteolytic
cleavage. The C-terminal glycine residue of the VP-molecule
is finally amidated.
In most mammals, VP contains an arginine residue at
position 8 (arginine vasopressin, AVP) and a five-membered
ring formed by a disulfide bridge between the
cysteine residues at position 1 and 6 ( Fig. 18-14 ). In the
members of the pig family, VP contains a lysine residue at
position 8. The lysine vasopressin (LVP) is the only form
present in the domestic pig. Heterozygotic peccaries, warthogs,
and hippopotami may possess both AVP and LVP.
Substitution of the phenylalanine residue at position 3 by
isoleucine leads to arginine vasotocin (AVT). This peptide
has been identified as a uniquely nonmammalian substance
and is probably the most primitive and certainly the most
commonly occurring neurohypophyseal peptide.
3. Secretion
The major determinant in the release of vasopressin is plasma
osmolality. Below a certain plasma osmolality threshold,
which may vary considerably between individuals, plasma
VP concentration is suppressed to levels that allow maximal
free water clearance ( Wade et al. , 1982 ). Once plasma
osmolality rises to the threshold, the pituitary secretes VP.
Although the concentration of plasma VP causing maximal
antidiuresis is about 5 to 10 pmol/liter, the release of VP is
related to plasma osmolality over a much broader range
(Robertson, 1983 ). Biewenga et al. , developed a nomogram
for this relationship in the dog, which allows analysis of the
osmoregulation of VP secretion in terms of sensitivity and
threshold ( Biewenga et al. , 1987 ). In healthy dogs, VP is
secreted in a pulsatile fashion with a wide variation in number
of pulses, VP pulse duration, and VP pulse amplitude
and height ( van Vonderen et al. , 2004b ). After water deprivation,
total and basal VP secretion, the number of significant
VP pulses, as well as the pulse characteristics, is not different
from basal values. However, during osmotic stimulation
with hypertonic saline, there is a large increase in both basal
and pulsatile VP secretion, and the number of VP pulses and
VP pulse height and amplitude increase significantly ( van
Vonderen et al. , 2004b ).
Apart from the influence of osmolality, a significant
decrease in circulating blood volume may also cause
enhanced VP secretion. The decrease in left atrial pressure
triggers receptors. Denervation of these receptors prevents
the hypovolemia-mediated VP release. The functional
properties of this regulatory system differ from those of the
osmoregulatory system. Although the relationship between
plasma osmolality and VP appears to be linear, the relationship
between blood volume and plasma VP is best described
by an exponential function ( Vokes and Robertson, 1985a ).
Under ordinary circumstances, changes in VP levels are
not observed until blood volume decreases by 5% to 10%.
With further decreases, plasma VP rises exponentially. The
relative insensitivity of VP to modest changes in blood volume
means that this regulatory mechanism plays little or no
role in the physiological control of water balance. Under
ordinary circumstances, total body water rarely changes
by more than 1% to 2%, an amount far too small to affect