Parathyroid hormone regulation of cytosolic Ca2+ in rat proximal tubules

Abstract

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)