Effects of Vasopressin and Water-Load on Urinary Adenosine-3',5'-Cyclic Monophosphate

Takahashi, Keiichi; Kamimura, Masahiro; Shinko, Takeshi; Tsuji, Soichi

doi:10.1016/s0140-6736(66)90568-x

Cited by 28 publications

(13 citation statements)

References 6 publications

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“…It is likely then that other factors significantly influence the rate of excretion of 3',5'-AMP in man. One report (33) showed that urinary 3',5'-AMP in man increased in response to vasopressin, an effect expected in view of the action of this hormone on adenyl cyclase in the renal medulla (3). However, for reasons unknown at present, this effect of vasopressin in vivo is small, and in several experiments of our own (Chase, Melson, and Aurbach, unpublished observations) no significant increase in urinary excretion of the nucleotide was detected after injection of vasopressin into normal subjects or patients with diabetes insipidus.…”

Section: Discussionmentioning

confidence: 99%

Pseudohypoparathyroidism: defective excretion of 3′,5′-AMP in response to parathyroid hormone

Chase¹,

Melson²,

Aurbach³

1969

J. Clin. Invest.

468

158

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A B S T R A C T Urinary excretion of cyclic adenosine 3',5'-monophosphate (3',5'-AMP) was tested in normal subjects and patients with pseudohypoparathyroidism, idiopathic hypoparathyroidism, surgical hypoparathyroidism, and pseudopseudohypoparathyroidism under basal conditions and after a 15 min infusion of purified parathyroid hormone. Basal excretion of the nucleotide was less than normal in the patients with hypocalcemic disorders and greater than normal in pseudopseudohypoparathyroidism. Parathyroid hormone caused a marked increase in excretion of 3',5'-AMP in all subjects except those with pseudohypoparathyroidism; nine patients with this disorder did not respond to the hormone and four showed a markedly deficient response. Radioimmunoassay showed that parathyroid hormone circulated in increased amounts in plasma from patients with pseudohypoparathyroidism and became undetectable when serum calcium was increased above 12 mg/100 ml. Suppression of parathyroid hormone secretion by induction of hypercalcemia did not alter the deficient response to exogenous hormone. The results indicate that: (a) parathyroid hormone circulates in abnormally high concentrations in pseudohypoparathyroidism and secretion of the hormone responds normally to physiological control by calcium; (b) testing urinary excretion of 3',5'-AMP in response to infusion of purified parathyroid hormone appears to-be an accurate and sensitive index for establishing the diagnosis of pseudohypoparathyroidism; and (c) the metabolic defect of the disorder can be accounted for by a lack of or defective form of parathyroid hormone-sensitive adenyl cyclase in bone and kidney.

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Section: Discussionmentioning

confidence: 99%

Pseudohypoparathyroidism: defective excretion of 3′,5′-AMP in response to parathyroid hormone

Chase¹,

Melson²,

Aurbach³

1969

J. Clin. Invest.

468

158

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“…The amount of vasopressin required exceeded the physiological range and was over 50-fold greater relative to body weight than the amount eliciting increased urinary 3'5'-AMP in man. 4 The low sensitivity of the rat to the effects of vasopressin makes it unlikely that the latter hormone was a significant influence in our experiments with parathyroid hormone. Moreover, the secretion of vasopressin was probably suppressed by the infusions given.…”

mentioning

confidence: 88%

Parathyroid function and the renal excretion of 3'5'-adenylic acid.

Chase¹,

Aurbach²

1967

Proc. Natl. Acad. Sci. U.S.A.

370

110

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Cyclic 3'5'-adeniylic acid (3'5'-AM1P) has been found1-4 in relatively high coIlceIltrttion in urine, but the physiological significance of this observation has not been completely elucidated. One report' indicated that the pituitary is not an important influence on the urinary excretion of cyclic adenylate in rats, and another4 showed that in man excretion of the cyclic nucleotide is stimulated by injection of vasopressin and suppressed when secretion of this neurohypophyseal hormone is inhibited.We have found that physiological amounts of parathyroid hormone cause a striking increase in urinary excretion of 3'5'-A1\IP through a direct action of the hormonal polypeptide on the kidney; this effect appears to be the earliest manifestation of the action of the hormone in vivo. These observations, outlined in this report, imply that the rate of secretion of parathyroid hormone is a major physiological factor affecting urinary 3'5'-AMP and suggest the possibility that cyclic adenylate is involved in the mechanism of action of the hormone.Materials and Methods.-Cyclic 3'5'-AMP-H' (1000 mc/mmole) was obtained from Schwarz Bioltesearch; 3'5'-AMP-C"4 (22 mc/mmole) was purchased from New England Nuclear Corp. Carrier-free purified radiophosphate was the product of Tracerlab Corp. Other reagents used, including the tricyclohexyl-ammonium salts of phosphoenolpyruvate and 3-phosphoglycerate, were the best grade available from standard suppliers. Stock crystalline preparations of pyruvate kinase, 310 U/mg; phosphoglycerate kinase, 250 U/mg; muscle glyceraldehyde-3-phosphate dehydrogenase, 40 U/mg; and myokiisase, 360 U/mg, were dialyzed against 4000 ml of 10-3 M Tris-ethylenediaminetetraacetate (Tris-EDTA), pH 7.5, quick-frozen (acetone-solid CO2 bath) in small portions, and stored at -200. Cyclic nucleotide phosphodiesterase from bovine heart was purified according to Butcher and Sutherland1 and stored in small aliquots frozen in liquid nitrogen; 1 ,.l of the enzyme solution catalyzed the conversion of 29.6 nmoles of 10-3 M cyclic adenylate to 5'-AMIP in 30 min at 30°in 1 ml at pH 7.5. Pure bovine parathyroid hormone (PTH), 2000-3000 USP U/mg, was prepared as described previously.5 Chromatographically purified corticotropin was the product of Sigma Chemical Co. Purified thyrocalcitonin was a gift of Dr. Paul Munson, and arginine vasopressin was the gift of Dr. Martin Petersen. Glucagon was purchased from Eli Lilly Co.Male or female Sprague-Dawley rats weighing 140-200 gm were allowed free access to water and standard laboratory chow until the beginning of the experiment. The animals, conscious throughout the tests, were held in restraining cages and given intravenous fluid pumped at a constants rate, usually 5 ml per hour, through a catheter in the external jugular vein or a needle in a tail vein. Infusion at this rate was begun 12-16 hr before the experimental tests and could be continued for longer than 48 hr without causing edema, gain in weight, or changes in the electrolytes of the serum. The fluid given contained 4% gl...

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“…Cyclic AMP has been found in dog plasma (1), and we have identified both cyclic nucleotides in human plasma, raising the possibility that renal plasma clearance could account for at least a portion of the cyclic nucleotides excreted into the urine. Two hormones known to stimulate renal adenyl cyclase systems (4) have been reported to increase cyclic AMP excretion (5,6) suggesting the kidney as a source of urinary cyclic AMP. Similarly, the kidney has been suggested as a source of urinary cyclic GMP (7).…”

Section: Introductionmentioning

confidence: 99%

Kinetic parameters and renal clearances of plasma adenosine 3′,5′-monophosphate and guanosine 3′,5′-monophosphate in man

Broadus¹,

Kaminsky²,

Hardman³

et al. 1970

J. Clin. Invest.

253

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A B S T R A C T Kinetic parameters and the renal clearances of plasma adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) were evaluated in normal subjects using tritium-labeled cyclic nucleotides. Each tracer was administered both by single, rapid intravenous injection and by constant intravenous infusion, and the specific activities of the cyclic nucleotides in plasma and urine were determined.Both cyclic AMP and cyclic GMP were cleared from plasma by glomerular filtration. The kidney was found to add a variable quantity of endogenous cyclic AMP to the tubular urine, amounting to an average of approximately one-third of the total level of cyclic AMP excreted. Plasma was the source of virtually all of the cyclic GMP excreted.Plasma levels of the cyclic nucleotides appeared to be in dynamic steady state. The apparent volumes of distribution of both nucleotides exceeded extracellular fluid volume, averaging 27 and 38% of body weight for cyclic AMP and cyclic GMP, respectively. Plasma production rates ranged from 9 to 17 nmoles/min for cyclic AMP and from 7 to 13 nnmoles/min for cyclic GMP. Plasma clearance rates averaged 668 mln/in for cyclic AMP and 855 ml/min for cyclic GMP. Approximately 85% of the elimination of the cyclic nucleotides from the circulation was due to extrarenal clearance.These studies were presented in part at the Annual Meeting of the Southern Society for Clinical Investigation, New Orleans, La., January, 1970. Clin. Res. 18: 73. (Abstr.) INTRODUCTION Adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) were identified in urine several years ago (1-3), but definitive studies concerning the sources of the excreted cyclic nucleotides have not been reported. Cyclic AMP has been found in dog plasma (1), and we have identified both cyclic nucleotides in human plasma, raising the possibility that renal plasma clearance could account for at least a portion of the cyclic nucleotides excreted into the urine. Two hormones known to stimulate renal adenyl cyclase systems (4) have been reported to increase cyclic AMP excretion (5, 6) suggesting the kidney as a source of urinary cyclic AMP. Similarly, the kidney has been suggested as a source of urinary cyclic GMP (7). In the absence of definitive clearance studies, it has not been possible to know whether the cyclic nucleotides in urine are derived solely from the kidney, solely from plasma, or both from plasma and from the kidney.The present studies were designed to evaluate the renal clearances as well as other kinetic parameters of the extracellular cyclic nucleotides. Tracer doses of tritiumlabeled cyclic nucleotides were administered to human subjects by rapid intravenous injection and by constant intravenous infusion. Specific radioactivity determinations of the cyclic nucleotides in plasma and urine provided information regarding the sources of cyclic AMP and cyclic GMP excreted into the urine. The effects of certain hormones on plasma and urinary cyclic nucleotides are repo...

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Effects of Vasopressin and Water-Load on Urinary Adenosine-3',5'-Cyclic Monophosphate

Cited by 28 publications

References 6 publications

Pseudohypoparathyroidism: defective excretion of 3′,5′-AMP in response to parathyroid hormone

Pseudohypoparathyroidism: defective excretion of 3′,5′-AMP in response to parathyroid hormone

Parathyroid function and the renal excretion of 3'5'-adenylic acid.

Kinetic parameters and renal clearances of plasma adenosine 3′,5′-monophosphate and guanosine 3′,5′-monophosphate in man

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