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Am J Physiol Renal Physiol 258: F545-F552, 1990;
0363-6127/90 $5.00
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AJP - Renal Physiology, Vol 258, Issue 3 545-F552, Copyright © 1990 by American Physiological Society


ARTICLES

Parathyroid hormone regulation of cytosolic Ca2+ in rat proximal tubules

C. R. Filburn and S. Harrison
Laboratory of Biological Chemistry, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224.

The effect of parathyroid hormone (PTH) on cytosolic Ca2+ was studied on suspensions of purified rat renal proximal tubules using the fluorescent indicator quin-2. Rat PTH-(1-34) produced a transient 40% increase in apparent cytosolic Ca2+ at 20 s, followed by a rapid return toward the basal level. The half-maximal dose for both the rate of rise and peak apparent Ca2+ was 3 X 10(-8) M for rat PTH-(1-34). Unlike PTH, forskolin and dibutyryl adenosine 3',5'-cyclic monophosphate had no immediate effect. Bovine PTH-(3-34) blocked the effect of PTH in a concentration-dependent manner. Acute reduction of medium Ca2+ to less than 10(-6) M had no effect on either PTH- or angiotensin II (ANG II)-induced transients, but prevented any sustained increases. Washing tubules in nominally Ca2(+)-free medium followed by ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid reduced both transients by 50%. PTH at 2 X 10(-7) caused small (6-9%) increases in accumulation of [3H]inositol phosphates comparable with that produced by norepinephrine at 10(-7) M. At 10(-7) M, norepinephrine produced increases in Ca2+ and inositol phosphates similar to PTH; at 10(-5) M much larger increases in inositol phosphates occurred. Exposure to high levels of either norepinephrine or ANG II before PTH administration prevented any subsequent stimulation by PTH or other agonists. A submaximal dose of norepinephrine only slightly blunted the effect of PTH or ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)


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