Plasma adenosine 3′,5′ -cyclic monophosphate in human hypertension

In a previous study we observed an increase in urinary cyclic AMP in labile hypertension in the upright position and during isoproterenol infusion, in contrast to a decrease in control subjects. In the present study we measured the plasma level of cyclic AMP in control subjects and patients with various types of hypertension. We obtained the following results: (1) plasma cyclic AMP increases in response to upright posture in control subjects and hypertensive patients; (2) values of cyclic AMP in the recumbent and upright positions are comparable in control subjects and patients with essential hypertension, but are significantly higher in those with true renovascular hypertension due to bilateral renal artery stenosis; (3) propranolol inhibits the increase of plasma cyclic AMP in response to posture in control subjects, but has an opposite effect in labile hypertension where there is a further increase; (4) the rise in blood pressure in pheochromocytoma is associated with a considerable increase in plasma cyclic AMP.Present and previous data suggest that kidney handling of cyclic AMP is abnormal in hypertension, and that the specific defect may be related to the type of hypertension.     

A simple radioimmunoassay for 3',5', cyclic adenosine monophosphate.

A radioimmunoassay for 3′,5′ cAMP has been developed in which [³H]3′,5′ cAMP is the radioligand. Antibody-bound and free fractions are separated with dextran-coated charcoal. The sensitivity of the assay is 0.03 pmoles and antiserum specificity is 7 orders with respect to other adenine nucleotides. Samples are prepared by ethanol precipitation. Tissue levels of 3′,5′ cAMP are comparable to those reported by others.     

Cyclic adenosine 3',5' monophosphate, calcium and protein phosphorylation in flagellar motility

cAMP and calcium are two important regulators of sperm flagellar motility. cAMP stimulates sperm motility by activating cAMP-dependent protein kinase and catalyzing the phosphorylation of sperm proteins. The stimulation of sperm motility by cAMP appears to be at two different levels. Evidence has been presented to suggest that cAMP-dependent phosphorylations may be required in order for motility to be initiated. In addition, cAMP-dependent phosphorylation appears to modulate specific parameters of motility resulting in higher beat frequency or greater wave amplitude. Calcium, on the other hand, when elevated intracellularly to 10(-6) M or higher, inhibits flagellar motility. The calcium-binding protein, calmodulin, appears to mediate a large number of effects of calcium on motility. Evidence suggests that calcium-calmodulin may be involved at the level of the membrane to pump calcium out of the flagellum. In addition, calcium-calmodulin may be involved in the control of axonemal function by regulating dynein ATPase and myosin light chain kinase activities. The identification of cAMP-dependent protein kinase, calmodulin and myosin light chain kinase in the sperm head suggests that cAMP and calcium-dependent phosphorylations are also involved in the control of the fertilization process, i.e., the acrosome reaction, in a manner similar to that known for the control of stimulus/secretion coupling. Finally, the effects of cAMP on flagellar motility are mediated by protein phosphorylation while the effects of calcium on motility are also in part, mediated by effects on protein phosphorylation.     

Hydrolysis of 2',3'-cyclic adenosine monophosphate and 3',5'-cyclic adenosine monophosphate in subcellular fractions of normal and neoplastic mouse spleen

A comparison has been made between the capacity to hydrolyse 2′,3′-cyclic adenosine monophosphate and 3′,5′-cyclic adenosine monophosphate in subcellular fractions of normal and neoplastic (lymphosarcoma) spleen of C₅₇BL mice. The effect of X-irradiation on these activities was tested. Subcellular fractionation of normal and lymphosarcoma spleen points to a different overall localization of the enzymes. The 2′,3′-cyclic nucleotide phosphodiesterase (2′,3′-cAMPase) has its highest specific activity in the particulate fractions of the cell, while the data on 3′,5′-cyclic nucleotide phosphodiesterase (3′,5′-cAMPase) show the highest activity in the soluble fraction. The 2′,3′-cAMPase activity is higher in the tumor as compared to the normal tissue, while the opposite holds for 3′,5′-cAMPase. Total body irradiation of normal mice with a dose of 600 rads of X-rays, results in a clear drop in 2′,3′-cAMPase 48 hours after the exposure. The 3′,5′-cAMPase is hardly affected at this time. Neither imidazol nor Mg⁺⁺ has any influence on the 2′,3′-cAMPase. The pH optimum for 3′,5′-cAMPase and 2′,3′-cAMPase appears to be 7.7 and 6.2 respectively. This report suggests a no-identity of the two enzymes in mouse spleen, a situation different from that found in certain plants.     

Occurrence of adenosine 3′:5′-cyclic monophosphate in plant tissues

A procedure is described which unequivocally demonstrates the presence of adenosine 3′:5′-cyclic monophosphate in Phaseolus vulgaris. Its concentration was determined spectrophotometrically at 2·6–9·2 nmol g^?1 of tissue (dry wt) for 6-day-old seedlings and about one-tenth of this in 13-day-old plants.     

Effects of adenosine 5'-monophosphate and adenosine 3',5'-cyclic monophosphate on l cells.

The adenine nucleotides, 5'-AMP and 3',5'-cyclic AMP block L cells in the S-phase of the cell cycle. The intracellular level of cyclic AMP is reduced after incubation of cells with 5'-AMP, and rates of uridine transport are increased after incubation with either 5'-AMP or cyclic AMP. On the contrary, cyclic AMP levels are increased and uridine transport decreased in cells treated with an inhibitor of the cyclic AMP phosphodiesterase. This inhibitor partially reverses the growth-inhibitory effect of cyclic AMP, indicating that a breakdown product is the effective inhibitor of growth. The inhibition of cell growth induced by the adenine nucleotides is prevented by uridine, suggesting that the block in S is due to a lack of availability of pyrimidines.     

Insulin-sensitive adenosine 3′,5′-cyclic monophosphate phosphodiesterase of hepatocyte plasma membrane

Adenosine 3′-,5′-cyclic monophosphate phosphodiesterase (EC 3.1.4.17) has been investigated in rat liver as to its insulin sensitivity. Hormone action has been assayed in vitro on a liver hemogenate purified by DEAE-cellulose column chromatography, on isolated hepatocytes, on isolaetd plasma membranes. The DEAE-cellulose chromatography purified homogenate showed no sensitivity to insulin, whereas isolated hepatocytes incubated in presence of insulin showed increased phosphodiesterase activity in a plasma membrane-containing fraction. The plasma membrane-bound enzyme, which shows both high and low affinity components, was significantly stimulated after hormonal treatment; this effect being dependent on a V increase of the low K_m form.     

Exercise-induced increases in myocardial adenosine 3′,5′-cyclic monophosphate and phosphodiesterase activity

Numerous cellular biochemical events caused by hormones are mediated throught cyclic AMP. Although many changes occur in the cell during exercise that could be attributed to this nucleotide, little evidence is available implicating it as an important regulator of exercise metabolism. In this investigation it was found that a 60 min bout of treadmill exercise caused a 2.4-fold increase in myocardial cyclic AMP immediately following the work. Rather than the imemediate nucleotide hydrolysis that was expected, it was found that the elevated cyclic AMP level remained for approx. 24 h before returning to control levels. Cardiac glycogen fell to 30% of control after work but supercompensated 60% above control within 1 h following exercise. Therefore, cardiac cyclic AMP was elevated at a time when glycogen was being synthesized. Study of the temporal relationship between the exercise-induced increase in cyclic AMP and cyclic nucleotide phosphodiesterase indicated that the work caused an increase in the hearts' capacity to hydrolyze cyclic AMP. Measurement of heart phosphodiesterase at substrate concentrations of 1.0 and 100 μM produced significant increased in enzyme activity immediately following exercise which remained elevated for 48 h and was back to control activity 96 h following work. These data present a potentially fascinating model for the study of the dissociation between cyclic AMP, glycogenesis and elevations in phosphodiesterase activity in the heart.     

Chlorpropamide and tolbutamide inhibition of adenosine 3'5' cyclic monophosphate phosphodiesterase

These sulfonylurea agents inhibit the cyclic AMP phosphodiesterase, and thereby could increase the steady state level of cyclic AMP in various tissues, depending upon the tissue concentrations achieved after oral or parental administration.     

Uptake and metabolism of 3′,5′-cyclic adenosine monophosphate and N,O′-dibutyryl 3′,5′-cyclic adenosine monophosphate in isolated bovine thyroid cells

1.

1. Accumulation of intracellular radioactivity was measured during incubation of isolated bovine thyroid cells with cyclic [³²P]AMP, cyclic [8-³H]AMP and dibutyryl cyclic [8-³H]AMP. With cyclic [³²P]AMP, ³²P cell/medium ratios ranged from 0 to to 0.04 compared to a maximum ³H cell/medium ratio of 0.29 with cyclic [³H]AMP and 0.16 with dibutyryl cyclic [³H]AMP. The excess of intracellular cyclic [³H] over cyclic [³²P]AMP radioactivity was due to extracellular formation of more penetrable dephosphorylated cyclic AMP metabolites which probably served as precursor of intra-cellular cyclic AMP.     

Exercise-induced increases in myocardial adenosine 3',5'-cyclic monophosphate and phosphodiesterase activity

Numerous cellular biochemical events caused by hormones are mediated through cyclic AMP. Although many changes occur in the cell during exercise that could be attributed to this nucleotide, little evidence is available implicating it as an important regulator of exercise metabolism. In this investigation it was found that a 60 min bout of treadmill exercise caused a 2.4-fold increase in myocardial cyclic AMP immediately following the work. Rather than the immediate nucleotide hydrolysis that was expected, it was found that the elevated cyclic AMP level remained for approx. 24 h before returning to control levels. Cardiac glycogen fell to 30% of control after work but supercompensated 60% above control within 1 h following exercise. Therefore, cardiac cyclic AMP was elevated at a time when glycogen was being synthesized. Study of the temporal relationship between the exercise-induced increase in cyclic AMP and cyclic nucleotide phosphodiesterase indicated that the work caused an increase in the hearts' capacity to hydrolyze cyclic AMP. Measurement of heart phosphodiesterase at substrate concentrations of 1.0 and 100 microM produced significant increases in enzyme activity immediately following exercise which remained elevated for 48 h and was back to control activity 96 h following work. These data present a potentially fascinating model for the study of the dissociation between cyclic AMP, glycogenesis and elevations in phosphodiesterase activity in the heart.     

Circadian variations in plasma 3':5'-cyclic adenosine monophosphate and 3':5'-cyclic guanosine monophosphate of normal adults.

Circadian variations in plasma cyclic AMP and cyclic GMP were studied in thirteen male subjects (20–22 years old) under controlled invironmental condition. Plasma collections were made every six hours. Cyclic AMP and cyclic GMP were determined by radioimmunoassay. Individual values of plasma cyclic AMP at 0800 are between 13.0 and 25.8 pmole/ml, and cyclic GMP between 2.5 and 7.0 pmole/ml. Cyclic AMP demonstrated the circadian variation with the maximum level at 1400 and the minimum at 0200, and cyclic GMP with the highest level at 1400 and the lowest level at 0800.     

Uptake of adenosine 3',5'-cyclic monophosphate and isoproterenol by filarial parasites

The filarial parasites Litomosoides carinii and Dipetalonema viteae both show transcuticular uptake of adenosine 3',5'-cyclic monophosphate but isoproterenol is taken up by D. viteae only. The importance of this difference is discussed from the point of view of metabolic regulation. Inhibition of uptake by lectins indicates the involvement of surface sugar moieties in the transport processes.     

Effects of ethanol on gastric mucosal adenosine 3', 5' monophosphate (cAMP)

The effects of ethanol on the gastric mucosal adenosine 3′, 5′-monophosphate (cAMP) system were evaluated. The activity of adenylate cyclase (AC), phosphodiesterase (PDE), and tissue content of cAMP were determined in the presence of ethanol. NaF stimulated AC in rat gastric mucosa was inhibited in vitro and in vivo by 20% ethanol. Basal AC activity was so low (0.05 ± 0.10 pmoles cAMP formed/min/mg protein) that consistent results without NaF could not be obtained. The PDE activity (172 ± 11 pmoles cAMP consumed/min/mg protein) was approximately 350 fold greater than the basal AC activity. All levels of ethanol tested (2.0–20.0%) significantly inhibited (p<0.05) PDE in vitro. Gastric mucosal levels of cAMP are not measurably altered by ethanol in vivo (5–20%).