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

Abstract

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...

Transport of Cyclic Nucleotides and Estradiol 17-β-d-Glucuronide by Multidrug Resistance Protein 4

“…A second proposed function for efflux is in provision of extracellular cAMP involved in intercellular signaling. This idea is consistent with the detection of cAMP in a variety of extracellular fluids (65)(66)(67) and is also supported by characterizations of cellular activities attributed to extracellular cAMP and presumably mediated by proteins located in the plasma membranes of target cells (see for example Refs. 68 -71).…”

Olmesartan Ameliorates Insulin Sensitivity by Modulating Tumor Necrosis Factor-.ALPHA. and Cyclic AMP in Skeletal Muscle

“…Although TNF-α was increased after 2 to 4 h of incubation, cAMP was not detected either in the incubation medium containing angiotensin II or in that containing vehicle as a control. This was a limitation of our experiment, since cAMP was quickly degraded ( 29 ), and unlike in the previous in vivo study, there was no supply of ATP in the present study. Therefore, we could not detect any cAMP in the medium after 2 to 4 h of incubation, and further experiments will thus be needed to investigate whether cAMP is produced by the soleus muscle in the presence of angiotensin II.…”

Sources of Cyclic Nucleotides in Plasma

“…(1), and that certain hormones can greatly alter the concentration of these cyclic nucleotides in plasma and urine (2)(3)(4)(5)(6)(7)(8). For example, cAMP levels in plasma and urine can be increased by the administration of parathyroid hormone (PTH) (3), glucagon (4), or epinephrine (4)(5)(6), and infusions of calcium (2) and norepinephrine (5,6) are each capable of elevating plasma and urinary cGMP.…”