Parathyroid hormone regulation of cytosolic Ca2+ in rat proximal tubules.
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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Laboratory of Biological Chemistry, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224.
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D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007295:Inositol Phosphates / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D007295:Inositol Phosphates; D010281:Parathyroid Hormone; D010446:Peptide Fragments; C058350:parathyroid hormone (7-34); D000804:Angiotensin II; D005576:Colforsin; C031617:parathyroid hormone (3-34); D003994:Bucladesine; D002118:Calcium; D009638:Norepinephrine