Plasma Cyclic AMP Levels Research Articles

The Cyclic AMP Response to Glucagon: Comparison of Tissue and Plasma Cyclic AMP Levels in the Rabbit

The effects of glucagon on tissue and plasma cyclic AMP levels have been investigated in rabbits anesthetized with urethane. Glucagon (2 nmole/kg.) caused at least a twofold increase in hepatic cyclic AMP, which reached a peak within two minutes and declined to basal values after 40 minutes. Plasma cyclic AMP also increased at least twofold, reaching a peak at 10 minutes and declining to basal values after 60 minutes. Glucagon (20 nmole/kg.) stimulated hepatic and plasma cyclic AMP in a manner indistinguishable from that observed at the lower dose. Hepatectomy abolished the plasma cyclic AMP responses to glucagon, and no significant stimulation of cyclic AMP concentration was noted in the heart, adipose tissue, small bowel, or kidney. Cyclic AMP hydrolysis was estimated in blood taken before and after administration of glucagon. Glucagon (2 nmole/kg.) increased cyclic AMP hydrolysis slightly, but this was explained by the raised cyclic AMP levels. By contrast, cyclic AMP hydrolysis increased two-to-threefold in blood taken 20 and 40 minutes after glucagon (20 nmole/kg.). The higher dose of glucagon also stimulated cyclic AMP hydrolysis in crude liver homogenate, which could not be explained by increases in cyclic AMP concentration. The increase in cyclic AMP hydrolysis observed in blood and liver may partly explain the failure to show additional stimulation of hepatic and plasma cyclic AMP levels with the higher dose of glucagon. Despite the changes in cyclic AMP hydrolysis, a highly significant correlation was observed in individual rabbits between the hepatic and plasma cyclic AMP responses to glucagon (2 and 20 nmole/kg.), when these were calculated as incremental areas above mean basal levels. It is suggested that measurement of plasma cyclic AMP levels after stimulation by glucagon may be an accurate index of the hepatic cyclic AMP response to glucagon in vivo.

The cyclic AMP response to glucagon. Comparison of tissue and plasma cyclic AMP levels in the rabbit

The cyclic AMP response to glucagon. Comparison of tissue and plasma cyclic AMP levels in the rabbit

ADRENOCEPTOR RESPONSIVENESS IN BRONCHIAL ASTHMA: EFFECT OF ISOPRENALINE INHALATION ON PLASMA CYCLIC 3′,5′‐AMP LEVELS

The effect of isoprenaline inhalation on plasma levels of cyclic AMP has been studied in a group of normal subjects and compared to a group of asthmatics. The normal subjects had a prompt rise in their plasma cyclic AMP level, and when compared to the asthmatic group, had a significantly greater percentage rise in plasma cyclic AMP from the basal levels. The markedly attenuated response to isoprenaline inhalation in the asthmatic group is consistent with the concept that asthmatics have a relative impairment of beta-adrenoceptor function. These results support the in vitro studies demonstrating that lymphocytes from asthmatic subjects incubated with isoprenaline produce less cyclic AMP than those from normal subjects.

Mechanism of plasma cyclic AMP response to hypoglycemia in man

The effect of insulin-induced hypoglycemia on plasma cyclic AMP levels was studied in normal volunteers, adrenalectomized, and sympathectomized subjects. Significant increases in plasma glucagon were observed in all groups. Normal subjects all had two- to threefold rises in plasma cAMP while no response was seen in any adrenalectomized or sympathectomized subject. These findings suggest that the mechanism for enhanced plasma cAMP release during insulin-induced hypoglycemia is catecholamine dependent. Glucagon does not contribute significantly to this response.

The effect of haloperidol on epinephrine-stimulated adenylate cyclase in humans

Administration of epinephrine in man has been shown previously to lead to a rise in plasma cyclic AMP levels by activation of the beta-adrenergic-stimulated adenylate cyclase. Therapeutic doses of lithium in humans block the epinephrine-induced rise in plasma cyclic AMP levels, suggesting that lithium inhibits beta-adrenergic adenylate cyclase. In contrast, ten subjects receiving haloperidol, a druh also effective in the treatment of mania, show a mean rise in plasma cyclic AMP levels after epinephrine administration and the magnitude of the response is the same as for non-drug treated individuals. These findings are discussed in relation to the possible pharmacological mechanisms of action of lithium and haloperidol in the control of mania.

Venous plasma cyclic AMP in acute cerebrovascular disease.

Antecubital venous blood was sampled from stroke patients in the presence of disodium ethylenediamine tetraacetate. Plasma was analyzed for cyclic AMP applying a competitive protein binding method without any special pretreatment. In mild hemispheric infarction as manifested by moderate hemiparesis and/or dysarthria, plasma cyclic AMP remained in the normal range (8-18 picomoles/ml). In most of the cases with moderate infarction, the cyclic AMP level was distinctly below the normal range several days after the onset of symptoms. However, cyclic AMP remained in the normal range in severe infarction with signs of brain edema, and in two cases with moderately severe symptoms. One of the two cases suffered from later development of brain edema, and the other revealed a large lesion in brain scintigrams. The sizes of the lesion revealed in brain scintigrams were smaller in the moderate cases and larger in the severe cases, except in one of the cases mentioned above. It appeared that with plasma cyclic AMP levels we could predict the extent of the lesion, and perhaps the subsequent development of impending brain edema in a few days after the onset of cerebral infarction. In moderate cases of cerebral hemorrhage, judged from the consciousness, cyclic AMP decreased to a subnormal level 2-4 days after the onset. In severe cases it remained in the normal range. Subarachnoid hemorrhage showed significantly elevated cyclic AMP levels in the early stage.

Studies on Adenylate Cyclase – Cyclic AMP System of the Myopathic Hamster (UM-X7.1) Skeletal and Cardiac Muscles

Cyclic AMP content, adenylate cyclase (EC 4.6.1.1) activity and phosphodiesterase I (EC 3.1.4.1) activity of the hind leg skeletal muscle and cardiac muscle in 60- and 150-day-old normal and myopathic (UM-X7.1) hamsters were examined. In 60-day-old myopathic animals, cardiac cyclic AMP levels were higher and phosphodiesterase I activity was lower, without any changes in the basal adenylate cyclase activity, whereas in 150-day-old myopathic hamsters, cardiac cyclic AMP and basal adenylate cyclase activity were lower, without any changes in the homogenate phosphodiesterase I activity. On the other hand, basal adenylate cyclase and phosphodiesterase I activities in the skeletal muscle homogenate from 60- and 150-day-old myopathic animals were not different from the normal values but the skeletal muscle cyclic AMP levels were significantly less in 60-day-old myopathic hamsters only. The plasma cyclic AMP levels in 60-day-old myopathic hamsters, unlike 150-day-old myopathic animals, were higher than the normal. Although these results reveal differences in myopathic cardiac and skeletal muscles, it is concluded that changes in adenylate cyclase-cyclic AMP system in myopathy are dependent upon the degree of disease.

Plasma cyclic AMP level in donors

The concentration of cyclic adenosine-3′,5′-monophosphate (cyclic AMP) in the plasma of blood donors (10 regular, 28 first time) was investigated by the competitive protein binding method on the day before donation and shortly after the removal of 20 ml blood. Two types of responses of the donors to donation were established: with no change and with a change in the cyclic AMP level. In accordance with these responses the donors were conventionally divided into two subgroups-“stable” and “reactive.” The cyclic AMP level in the regular donors was higher than in the primary, and at the time of taking the blood it was increased still more, especially among the subjects of “reactive” type. The cyclic AMP concentration in first-time donors of reactive type was either lower or higher than the mean value on the day before donation, and at the time of bleeding it rose or fell respectively to the mean level.

Studies of the elevated extracellular concentration of cyclic AMP in uremic man.

This study was designed to elucidate the mechanism of elevation of plasma cyclic AMP in uremic man. Plasma cyclic AMP was measured in 15 normal subjects and in 18 patients with severe renal failure. In some members from both groups the kinetic parameters of the metabolism of extracellular cyclic AMP were measured. Plasma cyclic AMP was elevated from 23 nM in control subjects to 59 nM in uremic patients, regardless of the presence or absence of the kidneys or parathyroid glands. A single pass of uremic blood through a Kiil hemodialyzer decreased plasma cyclic AMP from 58 to 30 nM. The clearance of cyclic AMP by the dialyzer correlated directly with the blood flow passing through the machine. Hemodialysis for 6 h decreased plasma cyclic AMP levels in the systemic circulation by only 12%. Studies with tritiated cyclic AMP revealed a plasma clearance rate of 624 ml/min in normal subjects and of 344 ml/min in patients with uremia. Such a large decrease in plasma clearance rate cannot be explained by a failure of urinary excretion of cyclic AMP and suggests impairment of "metabolic clearance." In addition, the "plasms production rate" of cyclic AMP was 65% higher in patients with renal failure than in normal subjects. It is concluded that the elevation of plasma cyclic AMP in uremic man is due to a combination of: (a) lack of urinary excretion, (b) decreases metabolic clearance, and (c) increased production of plasma cyclic AMP.

Myocardial and Plasma Levels of Adenosine 3′:5′-Cyclic Phosphate: Studies in Experimental Myocardial Ischemia

Alterations in myocardial and plasma levels of adenosine 3′:5′-cyclic phosphate (cyclic AMP) were studied following clamping of the aorta or coronary artery occlusion in 30 dogs. Plasma cyclic AMP levels increased markedly after thoracotomy but returned to control levels two hours later. Complete arrest of aortic flow (clamping) induced a significant early increase in the myocardial cyclic AMP levels of all animals studied. No increase was noted following pretreatment with propranolol or sham-occlusion. After localized coronary occlusion, only modest and insignificant changes occurred in plasma cyclic AMP levels in anesthetized animals and also in conscious dogs. The present study suggests that adrenergically mediated changes in tissue cyclic AMP content are an early manifestation of both generalized and local myocardial ischemia, while the plasma cyclic AMP level is a relatively insensitive indicator of small coronary occlusions.

Plasma cyclic adenosine 3′5′-monophosphate (AMP) levels in acute myocardial infarction

Plasma cyclic adenosine 3′5′-monophosphate (AMP) levels were measured in 44 patients with acute myocardial infarction, 33 patients with other cardiac and noncardiac diseases and 20 normal volunteers. The normal range of cyclic AMP was 4 to 16 picomoles/ml. The 35 surviving patients with acute myocardial infarction tended to have a slightly increased level of plasma cyclic AMP during the first 24 hours with a subsequent return to normal; the 9 nonsurvivors had abnormally high levels of cyclic AMP. An inverse correlation was found between cyclic AMP levels and stroke work index, and plasma cyclic AMP levels were of equal or better prognostic value than stroke work index. Plasma cyclic AMP levels were in the normal range in patients without acute myocardial infarction. Thus, very high levels of plasma cyclic AMP, found in patients with fatal myocardial infarction, appear to have clinical significance.