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Coordinated control of renal Ca(2+) transport proteins by parathyroid hormone.
[familial hypocalciuric hypercalcemia]
The
kidney
is
one
of
the
affected
organs
involved
in
the
clinical
symptoms
of
parathyroid
hormone
(
PTH
)
-
related
disorders
,
like
primary
hyperparathyroidism
and
familial
hypocalciuric
hypercalcemia
.
The
molecular
mechanism
(
s
)
underlying
alterations
in
renal
Ca
(
2
+
)
handling
in
these
disorders
is
poorly
understood
.
Parathyroidectomized
and
PTH
-supplemented
rats
and
mice
infused
with
the
calcimimetic
compound
NPS
R-
467
were
used
to
study
the
in
vivo
effect
of
PTH
on
the
expression
of
renal
transcellular
Ca
(
2
+
)
transport
proteins
,
including
the
epithelial
Ca
(
2
+
)
channel
transient
receptor
potential
,
vanilloid
,
member
5
(
TRPV
5
)
,
calbindins
,
and
the
Na
(
+
)
/
Ca
(
2
+
)
-
exchanger
(
NCX
1
)
.
In
addition
,
the
effect
of
PTH
on
transepithelial
Ca
(
2
+
)
transport
in
rabbit
connecting
tubule
/
cortical
collecting
duct
(
CNT
/
CCD
)
primary
cultures
was
determined
.
Decreased
PTH
levels
in
parathyroidectomized
rats
or
NPS
R-
467
-
infused
mice
,
resulted
in
reduced
expression
of
these
proteins
,
which
is
consistent
with
diminished
Ca
(
2
+
)
reabsorption
,
causing
the
development
of
the
observed
hypocalcemia
.
PTH
supplementation
of
parathyroidectomized
rats
restored
the
expression
of
the
renal
Ca
(
2
+
)
transport
machinery
and
serum
Ca
(
2
+
)
levels
,
independent
of
serum
1
,
25
-
dihydroxyvitamin
D
(
3
)
levels
and
renal
vitamin
D
or
Ca
(
2
+
)
-
sensing
receptor
mRNA
abundance
.
Inhibition
of
the
PTH
-stimulated
transepithelial
Ca
(
2
+
)
transport
by
the
TRPV
5
-
specific
inhibitor
ruthenium
red
reduced
the
PTH
-stimulated
expression
of
calbindin-
D
(
28
K
)
and
NCX
1
in
rabbit
CNT
/
CCD
primary
cultures
.
PTH
stimulates
renal
Ca
(
2
+
)
reabsorption
through
the
coordinated
expression
of
renal
transcellular
Ca
(
2
+
)
transport
proteins
.
Moreover
,
the
PTH
-induced
stimulation
is
enhanced
by
the
magnitude
of
the
Ca
(
2
+
)
influx
through
the
gatekeeper
TRPV
5
,
which
in
turn
facilitates
the
expression
of
the
downstream
Ca
(
2
+
)
transport
proteins
.
Therefore
,
the
renal
transcellular
Ca
(
2
+
)
transport
proteins
,
including
TRPV
5
,
could
contribute
to
the
pathogenesis
of
PTH
-related
disorders
.
Diseases
Validation
Diseases presenting
"which is consistent with diminished ca"
symptom
familial hypocalciuric hypercalcemia
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