Differential expression of angiotensin ii receptors during early
renal morphogenesis.
Norwood, Victoria F., Matthew R. Craig, J. Mansel Harris, R. Ariel
Gomez.
University of Virginia, Children's Medical Center, Charlottesville,
Virginia, USA 22908
APStracts 3:0353R, 1996.
Angiotensin II (Ang II) and its receptors, AT-1 and AT-2, may modulate
kidney development. To define the temporal and spatial distribution
of AT-1 and AT-2 receptors and their mRNAs during nephrogenesis,
fetal, newborn, and adult rat kidneys were studied using RT-PCR and
radioligand binding autoradiography. AT-1 expression was minimal at
E14, highly expressed at E20, and persisted into adulthood.
Conversely, AT-2 expression was easily detected from E14 through
postnatal day 7, but was undetectable by postnatal day 28. At E14,
76% of the receptors were AT-2, 24% were AT-1, and both were found in
the undifferentiated mesenchyme. By E17, AT-1 comprised 40% of the
receptors and localized to mature nephron segments while AT-2
remained within both condensed mesenchyme and differentiating
epithelia. The dissociation constants (KD) for AT-1 and AT-2 were
0.45+0.09 nM and 0.73+0.15 nM respectively at E17, similar to adult
values. By E20, AT-1 and AT-2 colocalized to the outer medullary
stripe, deep nephrons, medullary rays, and blood vessels while AT-2
continued to predominate in the actively differentiating cortex. The
presence of both subtypes of receptors capable of binding Ang II
during early nephrogenesis and the time-dependent and structure
-specific regulation of receptor localization confirms a regulated
developmental program for receptor expression and suggests important
roles for AT-1 and AT-2 in renal morphogenesis.
Received 16 January 1996; accepted in final form 5 September
1996.
APS Manuscript Number R25-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996