Plasma Concentrations Of Cyclic AMP Research Articles

Effect of surgical trauma on plasma concentrations of cyclic AMP and cortisol

The response of plasma cortisol and cyclic AMP concentrations to surgical trauma was examined in 7 general surgical patients. Five patients made uncomplicated recoveries and showed peak cortisol levels at 6 hours postoperatively, returning to normal by 24 hours. On patient developed postoperative pneumonia and the plasma cortisol remained elevated up to 48 hours, and the final patient showed no cortisol response at all. The plasma cyclic AMP concentrations showed a consistent rise during the operation itself, which was statistically significant when compared with preoperative levels (P less than 0.0125). Concentrations had fallen to normal by 6 hours in all the cases, except in the patient who developed pneumonia, where the plasma cyclic AMP also showed a prolonged elevation. The significance of these findings requires further elucidation, but the temporal relationship of the cyclic AMP and cortisol peaks would support the hypothesis that cyclic AMP may play a part in the mediation of ACTH release following surgical trauma.

Cyclic AMP, adrenaline and noradrenaline in plasma during surgery

Plasma concentrations of cyclic AMP, adrenaline and noradrenaline were measured in 6 patients undergoing hysterectomy from before induction of anaesthesia to 6 h after skin incision. Noradrenaline did not vary significantly during the observation period, whereas cyclic AMP and adrenaline increased after skin incision. A significant correlation was found between plasma concentrations of cyclic AMP and adrenaline (r = 0.84, P less than 0.01), suggesting that the latter is responsible for the increase in plasma cyclic AMP which is observed in relation to surgical procedures. Peak concentrations of cyclic AMP and adrenaline were seen in the early postoperative phase. This indicates that the most pronounced acute endocrine stress response to surgery of moderate severity occurs after termination of anaesthesia.

Changes in Plasma Cyclic AMP and Cyclic GMP during Spontaneous Labor and Labor Induced by Oxytocin, Prostaglandin F<sub>2</sub><sub>α</sub> and Prostaglandin E<sub>2</sub>

To investigate the response of cyclic nucleotides to the oxytocic agents administered for induction of labor, plasma concentrations of cyclic AMP (cAMP) and cyclic GMP (cGMP) were determined by radioimmunoassay during spontaneous labor and labor induced by oxytocin (OT), prostaglandin F2 alpha (PGF2 alpha), or PGE2 (PGE2). Subjects were 7 Japanese women in each labor group. Plasma cAMP levels significantly rose at the time of crowning of the fetal head in all 4 groups. They did not increase until that time in the 3 labor groups (spontaneous, OT-induced, and PGF2 alpha-induced labor groups). In the PGE2-induced labor group, plasma cAMP levels were significantly higher at labor onset (mean +/- SEM = 16.5 +/- 1.3 pg/ml) when compared to the pretreatment values (13.7 +/- 1.0 pg/ml), and increased thereafter gradually toward the time of crowning of the head (26.3 +/- 2.0 pg/ml). Plasma cGMP levels in the OT-induced group significantly rose after the onset of labor and remained at a high level until expulsion of the fetus. Plasma cGMP levels in the other groups did not change significantly throughout labor. These results suggest that cAMP may be involved in the labor process induced by PGE2, and that cGMP may be in that induced by OT.

Ovarian steroids modulate the action of calcitonin in women

Slow i.v. infusion of salmon calcitonin into normal women led to a transient increase in plasma concentrations of cyclic AMP and to a decrease in plasma calcium, which was maintained for at least 2 h. These responses were significantly reduced in the same patients after hysterectomy and ovariectomy. In contrast, maintenance of the ovaries at the time of surgery, or substitutive hormonal therapy, seemed to restore the sensitivity to exogenous calcitonin, suggesting a permissive role of ovarian steroids in the effect of calcitonin. The most likely explanation for this phenomenon is that these hormones influence either the number of calcitonin receptors or the coupling of the receptors to the functional unit of bone adenylate cyclase.

Increased plasma concentration of cyclic GMP in atrial fibrillation.

Plasma concentration of cyclic nucleotides in patients with paroxysmal atrial fibrillation was determined by ultrasensitive radioimmunoassay on the day of attack and also the next day, following recovery to sinus rhythmus. The concentration of cyclic GMP in the plasma of patients with attacks of paroxysmal atrial fibrillation was significantly higher than in those with sinus rhythmus, but no significant difference in plasma concentration of cyclic AMP was observed.

Urinary cyclic AMP excretion in birds: Dependence on parathyroid hormone activity

The cyclic AMP response of avian kidney to parathyroid activity has been evaluated both in vitro and in vivo. The production of cyclic AMP by dispersed avian kidney cells was stimulated by bovine parathyroid hormone or by an extract of avian parathyroid glands. Intravenous infusion of bovine parathyroid hormone resulted in increased urinary excretion and plasma concentration of cyclic AMP, as well as increased plasma calcium and urinary phosphorus excretion. The increases in plasma and urinary cyclic AMP preceded those of plasma calcium and of phosphorus excretion. EDTA infusion resulted in a decrease in plasma calcium and an increase in urinary cyclic AMP excretion. After 10 days on a low-calcium diet, chickens exhibited a 4.5-fold increase in urinary cyclic AMP excretion. The results suggest that urinary cyclic AMP in chickens reflects PTH activity similar to some mammalian species.

Plasma cyclic AMP responses to adrenaline administration in patients with spinocerebellar degeneration, bronchial asthma, and diabetes mellitus--a preliminary report of a clinical test for detecting beta-adrenergic dysfunctions.

Plasma cyclic AMP responses to adrenaline administration in normal volunteers, patients with spinocerebellar degeneration, bronchial asthma, pulmonary emphysema, and diabetes mellitus were studied. Intramuscular administration of low doses (0.1--0.4 mg/person) of adrenaline caused a dose-dependent increase in plasma cyclic AMP. The increase in cyclic AMP was completely prevented by propranolol, while it was not affected by phentolamine or atropine. In patients with spinocerebellar degeneration, the concentrations of plasma cyclic AMP both before and after adrenaline administration were lower than in normal subjects. In asthmatic patients, the plasma cyclic AMP increase after adrenaline administration was smaller than that of the healthy controls. The plasma concentration of cyclic AMP in patients with insulin-dependent diabetes reached the peak level more slowly than in diabetic patients with dietary control alone. Examining changes in the plasma cyclic AMP level after adrenaline administration appears to be a useful means for assessing the degree of beta-adrenergic dysfunction.

Changes in plasma cyclic nucleotides levels during various acute physical stresses.

Studies were performed with healthy volunteers to determine the effects of various stresses known to increase sympathetic nerve activity on the plasma concentration of cyclic AMP and cyclic GMP. Plasma cyclic AMP rose promptly in response to exercise; the elevation was completely abolished by a simultaneous injection of propranolol. Plasma cyclic GMP rose slightly after exercise; the elevation was completely abolished by a simultaneous injection of atropine. No significant changes occurred during tilting and cold pressor stress. The increase in plasma concentrations of cyclic AMP and cyclic GMP may serve as putative indices for beta-adrenergic, and cholinergic functions respectively during exercise of humans.

A multivariate factor analysis of the high plasma concentration of cyclic AMP in patients with chronic renal failure

The concentration of cyclic AMP which is known as an intracellular mediator of hormone action increased in the plasma of patients with chronic renal failure (CRF). In the present study, the plasma concentration of cyclic AMP significantly correlated not only with serum, creatinine, and urea levels, but also with plasma PTH and glucagon in patients with CRF. Furthermore, plasma concentrations of PTH and glucagon correlated with the serum creatinine concentration to a significant extent. To discuss the cause of the increased cyclic AMP concentration in plasma of patients with CRF, multivariate analyses were carried out on the obtained clinical data from patients and normal subjects. In the factor analysis on the clinical data from 61 subjects, cyclic AMP, creatinine and BUN correlated with the first factor and PTH correlated with the second factor. The cumulative contribution ratio by the second factor was 76%. The results of the cluster analysis indicated that cyclic AMP, creatinine, and BUN formed a cluster and PTH glucagon made another cluster. These results suggest that the elevated plasma concentration of cyclic AMP in patients with CRF was mainly introduced not by overproduction but by the retention of cyclic AMP due to the decreased renal function.

Species differences in the effect of parathyroid hormone on cyclic amp production

Abstract o 1. The effects of injected parathyroid hormone on the renal excretion of cyclic AMP and on its plasma concentration have been studied in chicken, goose, rabbit, pig, calf and man. 2. The amplitude of the peak plasma cyclic AMP response to a single injection of parathyroid hormone showed considerable differences between the species examined especially when a large dose of the hormone was used. The response shown by calves, aged 2 days to 6 weeks, was particularly poor. A sigmoid dose response curve was obtained in a human subject on measuring the maximum plasma cyclic AMP concentration in response to injected parathyroid hormone. 3. In general, there was no obvious relationship between plasma concentrations of cyclic AMP and its excretion rate by the kidneys but in the calf both parameters were low. Similarly, there appeared to be no simple relationship between extracellular cyclic AMP concentration and the phosphaturic response to the administration of parathyroid hormone.

Increased plasma cyclic AMP concentrations in fasting man

Plasma concentrations of adenosine 3', 5' monophosphate (cyclic AMP), free fatty acids (FFA), glycerol and glucose were measured after 24, 48 and 72 h fasting in healthy male students. There was a marked rise in plasma concentrations of cyclic AMP, FFA and glycerol from 24 to 48 h fasting with no further changes from 48 to 72 h fasting. Plasma glucose concentrations fell. After 72 h fasting, inhibition of adipose tissue lipolysis with a nicotinic acid analogue effected no significant change in plasma cyclic AMP concentrations, indicating that the elevated plasma nucleotide concentrations during fasting were not related to stimulation of lipolysis.

Effect of Salmon Calcitonin on Renal Excretion of Adenosine 3',5' Monophosphate in Man

Intravenous infusion of salmon calcitonin in six healthy subjects produced an increase in the plasma levels and urinary excretion of cyclic AMP. Cyclic AMP clearance diminished but remained higher than inulin clearance. Salmon calcitonin was also infused in six hypertensive patients with normal glomerular filtration rate. Arterial and renal venous plasma concentration of cyclic AMP were clearly raised. The difference between both these concentrations was not significant in the control periods but became marked during the treatment and post treatment periods demonstrating a net extraction of cyclic AMP from plasma by the kidneys. Renal extraction of cyclic AMP was lower than its urinary excretion in the control periods whereas it was clearly higher after salmon calcitonin was given. This shows that salmon calcitonin stimulates the production of cyclic AMP in extra-renal tissues and that the excess of cyclic AMP formed is catabolized by the kidneys.

Urinary and Plasma Cyclic Adenosine 3′,5′-Monophosphate in Patients with Idiopathic Edema

Urinary excretion and plasma concentrations of adenosine 3',5'-monophosphate were determined in idiopathic edema patients both at rest and after assumption of the upright position. Patients and normal subjects responded similarly to upright posture with decreases in urinary volume and creatine excretion and their urinary excretion of cyclic AMP was not significantly different. The plasma concentration of cyclic AMP was high in patients, both in the recumbent and upright positions, and its renal clearance (unlike that of creatinine) was low. Plasma cyclic AMP increased in response to upright posture both in patients and normal subjects. Even if the significance of elevated plasma cyclic AMP is unknown, its presence without an increase in urinary cyclic AMP suggests that the renal handling of cyclic AMP is abnormal is idiopathic edema; this may be related to an excessive beta-adrenergic tone.

The Sources of Plasma Cyclic AMP: Studies in the Rat using Isoprenaline, Nicotinic Acid and Glucagon

Abstract. The effects of intravenous administration of isoprenaline, glucagon and nicotinic acid on plasma concentrations of cyclic AMP in rats are described. In order to determine the relative importance of the liver as a source of extracellular cyclic AMP, the effects of the hormones were investigated in intact and functionally hepatectomised rats. The results showed that hepatectomy did not prevent an isoprenaline‐stimulated increase in plasma cyclic AMP concentrations, although glucagon was without effect on plasma nucleotide concentrations in this group of animals. It is suggested that the liver is essential for the action of glucagon but that isoprenaline can increase plasma cyclic AMP concentrations in hepatectomised animals by increasing extrahepatic release of the nucleotide. Since inhibition of adipose tissue lipolysis with nicotinic acid did not prevent an isoprenaline or glucagon‐stimulated increase in plasma cyclic AMP concentrations, adipose tissue is discounted as a major source of plasma cyclic AMP.

The Sources of Plasma Cyclic AMP: Studies in the Rat using Isoprenaline, Nicotinic Acid and Glucagon

The effects of intravenous administration of isoprenaline, glucagon and nicotinic acid on plasma concentrations of cyclic AMP in rats are described. In order to determine the relative importance of the liver as a source of extracellular cyclic AMP, the effects of the hormones were investigated in intact and functionally hepatectomised rats. The results showed that hepatectomy did not prevent an isoprenaline-stimulated increase in plasma cyclic AMP concentrations, although glucagon was without effect on plasma nucleotide concentrations in this group of animals. It is suggested that the liver is essential for the action of glucagon but that isoprenaline can increase plasma cyclic AMP concentrations in hepatectomised animals by increasing extrahepatic release of the nucleotide. Since inhibition of adipose tissue lipolysis with nicotinic acid did not prevent an isoprenaline or glucagon-stimulated increase in plasma cyclic AMP concentrations, adipose tissue is discounted as a major source of plasma cyclic AMP.

Plasma cyclic AMP and total catecholamines during acute myocardial infarction in man.

Abstract. There is marked alteration in endocrine activity during acute myocardial infarction (AMI). Many of the hormones involved act by changing target cell concentrations of adenosine 3′:5′ monophosphate (cyclic AMP). Since cyclic AMP can escape from cells, changes in intracellular concentrations of the nucleotide may be reflected in changes in plasma levels. The purpose of this study was to determine whether plasma cyclic AMP concentrations alter during the development of AMI.—Elevation of plasma cyclic AMP concentrations was noted during the first few hours following the onset of symptoms of AMI. The highest concentrations, recorded in a group of four patients with shock, showed a range of 54–193 pmol/ml which was significantly elevated compared to the normal range of 9–22 pmol/ml. This increase in plasma cyclic AMP correlated significantly and positively with plasma concentrations of total catecholamines. Patients with the worst prognosis had the highest plasma concentrations of cyclic AMP and total catecholamines.

Plasma Cyclic AMP and Total Catecholamines during Acute Myocardial Infarction in Man

Abstract. There is marked alteration in endocrine activity during acute myocardial infarction (AMI). Many of the hormones involved act by changing target cell concentrations of adenosine 3′: 5′ monophosphate (cyclic AMP). Since cyclic AMP can escape from cells, changes in intracellular concentrations of the nucleotide may be reflected in changes in plasma levels. The purpose of this study was to determine whether plasma cyclic AMP concentrations alter during the development of AMI.–Elevation of plasma cyclic AMP concentrations was noted during the first few hours following the onset of symptoms of AMI. The highest concentrations, recorded in a group of four patients with shock, showed a range of 54–193 pmol/ml which was significantly elevated compared to the normal range of 9–22 pmol/ml. This increase in plasma cyclic AMP correlated significantly and positively with plasma concentrations of total catecholamines. Patients with the worst prognosis had the highest plasma concentrations of cyclic AMP and total catecholamines.

Study on plasma cyclic nucleotide concentrations in fasting rats.

SummaryFasting in the rat for up to 120 hr does not change the plasma concentrations of cyclic AMP and cyclic GMP, although plasma glucose and free fatty acid concentrations are very markedly affected.

Effects of parathyroid hormone on plasma and urinary adenosine 3',5'-monophosphate in man.

The effects of parathyroid hormone (PTH) on plasma and urinary adenosine 3',5'-monophosphate (cyclic AMP) levels were studied in normal subjects. Under basal conditions normal adults have plasma concentrations of cyclic AMP ranging from 10 to 25 nmoles/liter and excrete from 1.5 to 5 mumoles of cyclic AMP per g of urinary creatinine. About one-half to two-thirds of the cyclic AMP excreted in the urine is derived from the plasma by glomerular filtration, and the remainder is produced by the kidney. Renal production of cyclic AMP is partly under the control of PTH. It can be suppressed by infusions of calcium and stimulated by infusions of the calcium chelating agent, EDTA. Infusions of PTH in doses up to 10 mU/kg per min were associated with dose-related increases both in urinary cyclic AMP and phosphate. Infusions of PTH in doses ranging from 20 to 80 mU/kg per min did not lead to any further increase in phosphaturia but did lead to further marked increases in urinary cyclic AMP. A modest increase in plasma cyclic AMP was noted when PTH was infused at 40 mU/kg per min. Anephric patients failed to show appreciable increases in plasma cyclic AMP in response to large doses of PTH but did show expected increases in response to glucagon. Surgical removal of parathyroid adenomas from nine patients with primary hyperparathyroidism was invariably followed by a decrease in urinary cyclic AMP, PTH, in large doses, and calcium infusion produced up to 2-fold increases in the other known naturally occurring cyclic nucleotide, guanosine 3',5'-monophosphate (cyclic GMP).