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

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Chapter | 18 Pituitary Function
VP secretion through hemodynamic influences ( Wang and
Goetz, 1985 ). In dogs, 24 h of fluid deprivation increases
plasma VP because of changes in both extracellular volume
and tonicity, but the increase in tonicity plays a greater role
than the reduction in volume ( Wade et al. , 1983 ).
It has been proposed that hemodynamic influences
modulate VP secretion by raising or lowering the osmostat
( Robertson, 1978 ). According to this concept, a decrease in
plasma volume or pressure will permit normal osmoregulation
of VP, but the threshold for release will be lowered
by an amount proportional to the degree of hypovolemia or
hypotension, associated with increased sensitivity of the VP
response to rising plasma osmolality. Conversely, hypervolemia
or hypertension increases the threshold and decreases
the sensitivity of release (Quillen and Cowley, 1983) .
There are numerous other factors that may influence
VP secretion. Of these, nausea/vomiting ( Rascher
et al. , 1986 ), insulin-induced hypoglycemia ( Vokes and
Robertson, 1985b ), and stress ( Jorgensen et al. , 2002 ) are
the most potent. The effects of opiates and opioid peptides
on VP secretion have been studied for many years and
have been the subject of some controversy. Both stimulatory
and inhibitory effects have been reported. Apart from
the substances, doses, and routes of administration used,
the animal species is an important factor ( Van Wimersma
Greidanus, 1987 ). Intracerebroventricular administration
of β -END in conscious rats decreases basal and stimulated
VP release ( ten Haaf et al. , 1986 ). An opioid inhibition of
dehydration-induced VP release has been reported in dogs
( Wade, 1985 ). However, Hellebrekers et al. , (1988) could
not confirm this endogenous opioid modulation of osmolality-regulated
VP release in conscious dogs subjected to
hypertonic saline infusion. In contrast, sharp increases in
plasma VP have been found in conscious dogs after intravenous
administration of the μ -type opiate receptor agonist
methadone ( Hellebrekers et al. , 1987 ).
In addition, a large number of drugs and hormones,
among which are glucocorticoids (inhibitory effect), angiotensin
II, and corticotropin-releasing factor (stimulatory
effect), influence VP secretion ( Berl and Robertson, 2000 ).
4 . VP Action and Aquaporin-2
The biological effects of VP are mediated by three receptor
subtypes: V1 receptors on blood vessels, V2 receptors
on renal collecting duct epithelia, and V3 receptors (also
termed V1b) responsible for the stimulation of adrenocorticotropin
from the AL ( Birnbaumer, 2000 ; Robinson and
Verbalis, 2003 ).
The major role of VP is to regulate body fluid homeostasis
by affecting water resorption. An increase in plasma VP
results in increased water retention, which maintains plasma
osmolality between narrow limits. The antidiuretic effect is
achieved by promoting the reabsorption of solute-free water
in the distal and collecting tubules of the kidney. In the
absence of VP, this portion of the nephron is not permeable
to water and the hypotonic filtrate of the ascending limb of
Henle’s loop passes unmodified through the distal tubule and
collecting duct. In this condition urine osmolality decreases
to around 80 mOsm/kg. Binding of VP to its V2 receptor in
collecting duct cell membranes initiates a signal transduction
cascade leading to an intracellular increase in cAMP
( Jard, 1983 ), activation of protein kinase A ( Deen et al. ,
2000 ), and subsequent phosphorylation of the water channel
protein, the so-called aquaporin-2. In the plasma membranes
of highly water-permeable cells, aquaporins (AQPs), a family
of integral membrane proteins, function as water-selective
channels ( Agre et al. , 2002 ; Deen et al. , 2000 ; Nielsen
et al. , 1995 ). Seven different renal AQPs (AQP 1-4, 6-8)
have been defined thus far, correlating with well-defined
segmental permeabilities in the nephron ( King and Yasui,
2002 ). Aquaporin-2 has been characterized as the major
VP-regulated water channel and is predominantly localized
in the apical membrane and the intracellular vesicles of collecting
duct principal cells ( Nielsen et al. , 1993 ). In the presence
of these water-selective channels, water can move passively
along an osmotic gradient—that is, from the distal and collecting
duct tubules to the hypertonic renal medulla. After
VP withdrawal, aquaporin-2 is redistributed into the cell and
water permeability decreases ( Nielsen et al. , 1995 ). Urinary
excretion of AQP2 closely parallels changes in VP exposure
and has been proposed as a reliable marker for collecting
duct responsiveness to VP in various physiological states of
water homeostasis as well as disorders of water homeostasis.
As in humans, urinary AQP2 excretion in dogs closely
reflects changes in VP exposure, elicited by water loading,
hypertonic saline infusion, and intravenous desmopressin
administration and is proposed as a marker for collecting
duct responsiveness to VP ( van Vonderen et al. , 2004c ).
Besides this well-known role in the regulation of fluid
homeostasis, VP exerts a large variety of effects. Among
these is the vasopressor effect, which is mediated by V1
receptors ( Liard, 1986 ). In addition, VP increases glucogenolysis
by liver cells, increases ACTH release by adenohypophysis
( Lowry et al. , 1987 ), and has several effects on
animal behavior ( de Wied and Versteeg, 1979 ). The extrarenal
effects on hepatocytes and vascular smooth muscle
are exerted through cAMP-independent, calcium-dependent
V1 receptors ( Jard, 1983 ).
There is some evidence that in birds AVT, apart from
its established antidiuretic action, also has oxytocic properties
and participates in normal oviposition ( Shimada et al. ,
1986, 1987 ). MT does not seem to function in oviposition
and its release was found to be negatively correlated with
plasma osmolality ( Koike et al. , 1986 ).
5 . Disease
Disorders of the hypothalamic-neurohypophyseal system
resulting in deficiency or excess of VP are known to occur