scholarly journals Parathyroid hormone regulates phosphate transport in OK cells via an irreversible inactivation of a membrane protein

FEBS Letters ◽  
1987 ◽  
Vol 216 (2) ◽  
pp. 257-260 ◽  
Author(s):  
Kerstin Malmström ◽  
Heini Murer
Keyword(s):  
Parathyroid Hormone ◽  
Membrane Protein ◽  
Phosphate Transport ◽  
Ok Cells

A dual mechanism for regulation of kidney phosphate transport by parathyroid hormone

1987 ◽  
Vol 253 (2) ◽  
pp. E221-E227 ◽  
Author(s):  
J. A. Cole ◽  
S. L. Eber ◽  
R. E. Poelling ◽  
P. K. Thorne ◽  
L. R. Forte
Keyword(s):  
Protein Kinase C ◽  
Parathyroid Hormone ◽  
Protein Kinase ◽  
Phorbol Esters ◽  
Rank Order ◽  
Phosphate Transport ◽  
Opossum Kidney ◽  
Ok Cells ◽  
Kinase C ◽  
Camp Formation

Regulation of phosphate transport by parathyroid hormone (PTH) was investigated in continuous lines of kidney cells. Phosphate transport was reduced by PTH-(1-34) at physiological concentrations (EC50 5 X 10(-11) M), whereas much higher concentrations were required to stimulate cAMP formation (EC50 1 X 10(-8) M) in opossum kidney (OK) cells. The PTH analogue [Nle]PTH-(3-34) also inhibited phosphate transport but did not enhance cAMP formation. Instead, [Nle]PTH-(3-34) was a competitive antagonist of PTH-(1-34) at cyclase-coupled receptors. PTH-(7-34) had no effect on phosphate transport or cAMP formation. Phorbol esters or mezerein were potent inhibitors of phosphate transport but did not affect cAMP synthesis. Their potencies paralleled the rank-order potency of these agents as activators of protein kinase c in other systems. Maximally effective concentrations of PTH-(1-34) and mezerein did not produce additive inhibition of phosphate transport in OK cells. Phorbol esters stimulated phosphate transport in JTC-12 cells, but PTH-(1-34) had no effect. We concluded that PTH regulates OK cell phosphate transport by interacting with two classes of receptors, and transmembrane-signaling mechanisms. Physiological levels of PTH-(1-34) may regulate phosphate transport by activation of protein kinase c, whereas higher concentrations appear to activate adenylate cyclase.

Parathyroid hormone inhibits phosphate transport in OK cells but not in LLC-PK1 and JTC-12.P3 cells

1986 ◽  
Vol 251 (1) ◽  
pp. C23-C31 ◽  
Author(s):  
K. Malmstrom ◽  
H. Murer
Keyword(s):  
Parathyroid Hormone ◽  
Cell Lines ◽  
Apical Membrane ◽  
Membrane Vesicles ◽  
Phosphate Transport ◽  
Continuous Cell Lines ◽  
Ok Cells ◽  
Regulatory Cascade ◽  
Regulatory Event ◽  
Apical Membrane Vesicles

Na+-dependent phosphate transport and its response to parathyroid hormone (PTH) has been investigated in three continuous cell lines of renal epithelial origin (LLC-PK1, JTC-12.P3, and OK). The apparent Km for phosphate was similar, but the maximal transport rate (Vmax) was markedly different in the three cell lines. PTH and forskolin produced an increase of cellular adenosine 3',5'-cyclic monophosphate (cAMP) in all cell lines, but Na+-dependent phosphate transport was inhibited exclusively in the OK cells (a threefold reduction of influx after 4 h of exposure to 10(-10) M PTH). The change in phosphate transport is accounted for by a lowered Vmax (30.8 +/- 5.3 vs. 10.2 +/- 1.1 pmol X mg-1 X 3 min-1). The reduction in phosphate transport was reversible, such that 5 h after removal of PTH the Vmax had increased threefold over the inhibited state. Addition of PTH did not alter Na+-dependent L-alanine influx in the OK cells. Experiments with apical membrane vesicles showed that the change in Vmax occurred at the membrane level. It is concluded that the regulatory event responsible for PTH-reduced phosphate transport is beyond cAMP. Of the cell lines studied, only OK cells have a complete regulatory cascade.

Effect of U-73,122, an inhibitor of phospholipase C, on actions of parathyroid hormone in opossum kidney cells

1994 ◽  
Vol 266 (2) ◽  
pp. F254-F258 ◽  
Author(s):  
K. J. Martin ◽  
C. L. McConkey ◽  
A. K. Jacob ◽  
E. A. Gonzalez ◽  
M. Khan ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Protein Kinase ◽  
Phospholipase C ◽  
Second Messengers ◽  
Cytosolic Calcium ◽  
Phosphate Transport ◽  
Response Curves ◽  
Opossum Kidney ◽  
Ok Cells ◽  
Opossum Kidney Cells

The relative roles of the adenylate cyclase-protein kinase A system (AC-PKA), the phospholipase C-protein kinase C system (PLC-PKC), and increases in cytosolic calcium in mediating the final actions of parathyroid hormone (PTH) remain ill defined. Although an important role for the PLC-PKC system in the regulation of phosphate transport in response to PTH has been suggested, previous studies from our laboratory and others, in OK cells, have emphasized the major role of AC-PKA. The present studies were designed to dissociate the second messengers for PTH by using an inhibitor of PLC (U-73,122). Studies were performed in confluent cultures of OK cells with and without preincubation with U-73,122 (1 microM). This inhibitor did not alter adenosine 3',5'-cyclic monophosphate (cAMP) production or the activation of PKA in response to PTH. Preincubation with U-73,122, however, totally abolished PTH-stimulated increases in diglyceride mass, consistent with inhibition of PLC. Activation of particulate PKC was then examined in response to PTH in the absence and presence of U-73,122. Although PTH resulted in an increase in particulate PKC activity in control cultures, this effect was abolished in the presence of U-73,122 and actually decreased significantly. Therefore, having documented marked attenuation of PLC-PKC, we next examined the effects of PTH on phosphate transport. Basal phosphate uptake was not altered by 1 microM U-73,122. Dose-response curves of the inhibition of phosphate transport in response to PTH were identical in the presence or absence of U-73,122. Thus inhibition of PLC and PKC activities did not alter the effects of PTH on phosphate transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Establishment of a Parathyroid Hormone-Responsive Phosphate Transport System in Vitro Using Cultured Renal Cells*

Endocrinology ◽  
1986 ◽  
Vol 119 (5) ◽  
pp. 1954-1963 ◽  
Author(s):  
YOSHIKAZU KINOSHITA ◽  
MASAAKI FUKASE ◽  
AKIMITSU MIYAUCHI ◽  
MUTSUMI TAKENAKA ◽  
MASAKI NAKADA ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Transport System ◽  
Phosphate Transport ◽  
Renal Cells

scholarly journals Mechanism of dopamine inhibition of renal phosphate transport.

1992 ◽  
Vol 2 (11) ◽  
pp. 1601-1607
Author(s):  
J Isaac ◽  
R P Glahn ◽  
M M Appel ◽  
M Onsgard ◽  
T P Dousa ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Brush Border Membrane ◽  
Phosphate Transport ◽  
Constant Infusion ◽  
Saline Control ◽  
Control Group ◽  
Sprague Dawley ◽  
Pi Transport ◽  
Sprague Dawley Rats ◽  
Dependent Transport

Dopamine (DA) is natriuretic and phosphaturic. However, whether the effect of DA on Pi reabsorption is a consequence of its effect on sodium transport is not known. Therefore, this study was performed to determine the effect of DA on the maximal transport of phosphate (TmPi), and upon the capacity of renal proximal brush border membrane (BBM) for (Naextra-vesicular greater than Naintravesicular)-gradient-dependent transport of Pi, as compared with the transport of other solutes. Graded infusions of Pi (0, 1, 2, and 3 mumols/min) were given to thyroparathyroidectomized male Sprague-Dawley rats in the presence of vehicle (0.9% NaCl; N = 5), DA 15 micrograms/kg/min; N = 6), or parathyroid hormone ((PTH); 1 U/kg/min; N = 5). The TmPi for rats infused with DA (3.3 +/- 0.3 mumol/mL) was significantly less than the TmPi for saline control rats (4.4 +/- 0.2 mumol/mL). Rats infused with PTH exhibited the lowest TmPi (1.8 +/- 0.3 mumol/mL). No differences in sodium excretion were observed among any of the groups. Na-dependent Pi transport was studied in BBM vesicles (BBMV) prepared from rats fed a low-phosphate diet for 2 days that were anesthetized, acutely thyroparathyroidectomized, and systemically infused with DA (350 micrograms bolus, plus 35 micrograms/kg/min; N = 8), PTH (33 U/kg bolus, followed by a continuous infusion of 1 U/kg/min; N = 6), or vehicle (1 mL/kg bolus, plus 2 mL/h constant infusion of 0.9% NaCl; N = 8) for 90 min. DA significantly inhibited the Na cotransport of Pi by 22.4 +/- 4.1% (P less than 0.01) as compared with the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Dopamine enhances the phosphaturic response to parathyroid hormone in phosphate-deprived rats.

1992 ◽  
Vol 2 (9) ◽  
pp. 1423-1429
Author(s):  
J Isaac ◽  
T J Berndt ◽  
S L Chinnow ◽  
G M Tyce ◽  
T P Dousa ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Fractional Excretion ◽  
Phosphate Transport ◽  
Dopamine Synthesis ◽  
Dopamine Infusion ◽  
Phosphate Deprivation ◽  
Dietary Phosphate ◽  
Urinary Dopamine ◽  
Fractional Excretion Of Phosphate ◽  
High Phosphate

Phosphate deprivation results in a resistance to the phosphaturic effect of parathyroid hormone. Dopamine is phosphaturic and is synthesized by kidney proximal tubule, the nephron subsegment where parathyroid hormone inhibits phosphate transport. Thus, to test the hypothesis that phosphate deprivation is associated with low intrarenal dopamine synthesis and that dopamine infusion will overcome the resistance to the phosphaturic response to parathyroid hormone, the following study was performed. The effect of dietary phosphate intake on intrarenal dopamine synthesis, as reflected by urinary dopamine excretion, was determined. Rats were placed in metabolic cages (N = 5) and were fed a low-phosphate diet (0.07% Pi) for 4 days and then a high-phosphate diet (1.8% Pi) for 4 days. Twenty-four-hour urinary dopamine excretion was significantly lower in rats fed a low-phosphate diet (2.53 +/- 0.06 versus 4.10 +/- 0.30 micrograms/day). Further, the effect of dopamine infusion on the blunted phosphaturic response to parathyroid hormone was studied in rats fed a low-phosphate diet for 1, 2, and 3 days. Control clearances were taken 2 h after thyroparathyroidectomy; then, parathyroid hormone (33 U/kg plus 1 U/kg/min), dopamine (25 micrograms/kg/min), or parathyroid hormone plus dopamine were infused for 60 min. Changes in the fractional excretion of phosphate were significantly greater in rats fed a low-phosphate diet infused with parathyroid hormone plus dopamine than in rats fed a low-phosphate diet infused with parathyroid hormone alone (delta 27.9 +/- 5.8 versus 11.2 +/- 2.6% for day 1; 28.4 +/- 1.4 versus 7.1 +/- 3.6% for day 2; and 10.7 +/- 2.8 versus -0.2 +/- 0.2% for day 3; N = 5 for all groups).(ABSTRACT TRUNCATED AT 250 WORDS)

Sign in / Sign up

Export Citation Format

Share Document