pyrophosphate and Pheochromocytoma

Protein phosphatases and phosphatase inhibitors were used to examine the role of protein phosphorylation in the regulation of norepinephrine secretion in digitonin-permeabilized PC12 cells. The addition of an exogenous type 2A protein phosphatase caused as much as a 70% decrease in Ca2(+)-dependent norepinephrine secretion. In the presence of okadaic acid, a potent inhibitor of type 2A protein phosphatases, phosphatase 2A had no effect on secretion. The addition of exogenous calcineurin, a Ca2(+)-calmodulin-stimulated phosphatase, also caused decrease in Ca2(+)-dependent secretion, but on a molar basis it was less effective than phosphatase 2A. Two phosphatase inhibitors, 1-naphthylphosphate and sodium pyrophosphate, caused 75-100% increases in the amount of norepinephrine secreted in the absence of Ca2+ without affecting the amount of norepinephrine secreted in the presence of Ca2+. This stimulation of Ca2(+)-independent secretion by 1-naphthylphosphate and pyrophosphate suggests that there is a slow rate of Ca2(+)-independent phosphorylation and that phosphorylation triggers secretion. Unlike the results obtained in the presence of ATP, secretion in the presence of adenosine-5'-O-(3-thiotriphosphate), ATP gamma S, was not affected by the addition of type 2A protein phosphatase or by the addition of phosphatase inhibitors. These results are consistent with secretion in these permeabilized cells being regulated by a Ca2(+)-stimulated phosphorylation.

Topics: Adenosine Triphosphate; Adrenal Gland Neoplasms; Animals; Calcium; Cell Line; Cell Membrane Permeability; Diphosphates; Ethers, Cyclic; Kinetics; Macromolecular Substances; Naphthalenes; Norepinephrine; Okadaic Acid; Organophosphorus Compounds; Pheochromocytoma; Phosphoprotein Phosphatases; Phosphorylation; Protein Phosphatase 2; Rats; Tumor Cells, Cultured

Myocardial scinitgrams, using 99mTc-stannous pyrophosphate, showed an acute posterior infarction and an abnormally placed left kidney in a 24-year-old hypertensive man; Further study revealed that the kidney was displaced by a mass later proven to be a pheochromocytoma. The latter was the cause of his hypertension and probably instigated the acute myocardial infarction.

Topics: Adult; Diphosphates; Humans; Hypertension; Kidney Diseases; Male; Myocardial Infarction; Pheochromocytoma; Radionuclide Imaging; Technetium