Increase In Plasma Cyclic AMP Research Articles

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.

A physiological response (plasma cyclic amp) and a psychological response (STAI-A-state) to noise exposure and/or calculation task

The effects of 90 dB(A) noise exposure and/or a calculation task on plasma cyclic AMP concentrations (physiological index) and STAI-A-State scores (psychological index) in normal subjects are compared. Neither the plasma cyclic AMP concentration nor the STAI-A-State scores showed any significant change in response to the calculation task. STAI-A-State scores increased significantly only in response to 90 dB(A) noise exposure, while both the indices showed significant increases under the effects of both noise exposure and the calculation task. The sensitivity of the rate of increase in plasma cyclic AMP caused by noise exposure plus the calculation task was higher than that of the rate of increase in scores on the A-State scale caused by this noise exposure/task combination. The physiological effect in human subjects of noise exposure became larger when a psychological stress (calculation task) was added.

Adrenaline Responsiveness in Borderline Hypertension

The effects of circulating adrenaline on cardiovascular function were studied in 14 subjects with borderline hypertension (BHT) and in 14 matched normotensive controls. Adrenaline was infused in stepwise increasing doses (0.1, 0.2, 0.4, and 0.8 nM/kg/min, i.v.). Noninvasive measurements of cardiac function (M-mode echocardiography) and blood pressure and blood sampling for determinations of venous plasma noradrenaline, adrenaline, cyclic AMP, and potassium were performed. Systolic and diastolic blood pressure responses to adrenaline were similar in both groups. Cardiac output was increased in BHT at rest but the signs of an increased myocardial contractility disappeared during adrenaline infusion. The BHT group displayed elevated heart rates and systemic vascular resistances over the full range of adrenaline concentrations studied but the responsiveness was similar in both groups. The beta 2-adrenoceptor-mediated increases in plasma cyclic AMP and decreases in plasma potassium were similar in the BHT and control groups. The results suggest an increased arousal in BHT at rest. Furthermore, beta 2-adrenoceptor sensitivity appears to be unaltered in BHT.

Plasma Cyclic Nucleotides in Spontaneously Hypertensive Rats: Hyperresponse to Acute Hot Stress

An acute hot stress caused a sharp increase in plasma cyclic AMP and cyclic GMP in both spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). This hot stress-induced increase in plasma cyclic AMP was observed even after chemical sympathectomy elicited by 6-hydroxydopamine or depleting the catecholamine stores in adrenergic neurons by tyramine or reserpinization, but was no longer observable after β-adrenergic blockade by propranolol, blockade of autonomic ganglia by hexamethonium, adrenodemedullation or anesthesia by pentobarbital. These results indicate that the initial stimulation of the central nervous system evoked the release of catecholamines from the adrenal medulla which could activate adenylate cyclase via the stimulation of β-adrenoceptors on the cell surface. The increment of plasma cyclic GMP was not influenced by prior blockade of the peripheral autonomic nervous system, but was totally abolished by pentobarbital, indicating that cyclic GMP generated within the central nervous system in response to the hot stress would be directly related to its increase in the peripheral blood stream. The plasma cyclic AMP and cyclic GMP responses were greater in adult SHR than in young SHR and young and matured WKY. The predominant response of plasma cyclic AMP might be due to a greater release of catecholamine from the adrenal medulla in matured SHR. The hyperresponse of plasma cyclic GMP in adult SHR remains to be fully elucidated. The increased cyclic nucleotide responses in SHR might be an important factor in the maintenance of hypertension.

Plasma cyclic nucleotides in spontaneously hypertensive rats: hyperresponse to acute hot stress.

An acute hot stress caused a sharp increase in plasma cyclic AMP and cyclic GMP in both spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). This hot stress-induced increase in plasma cyclic AMP was observed even after chemical sympathectomy elicited by 6-hydroxydopamine or depleting the catecholamine stores in adrenergic neurons by tyramine or reserpinization, but was no longer observable after beta-adrenergic blockade by propranolol, blockade of autonomic ganglia by hexamethonium, adrenodemedullation or anesthesia by pentobarbital. These results indicate that the initial stimulation of the central nervous system evoked the release of catecholamines from the adrenal medulla which could activate adenylate cyclase via the stimulation of beta-adrenoceptors on the cell surface. The increment of plasma cyclic GMP was not influenced by prior blockade of the peripheral autonomic nervous system, but was totally abolished by pentobarbital, indicating that cyclic GMP generated within the central nervous system in response to the hot stress would be directly related to its increase in the peripheral blood stream. The plasma cyclic AMP and cyclic GMP responses were greater in adult SHR than in young SHR and young and matured WKY. The predominant response of plasma cyclic AMP might be due to a greater release of catecholamine from the adrenal medulla in matured SHR. The hyperresponse of plasma cyclic GMP in adult SHR remains to be fully elucidated. The increased cyclic nucleotide responses in SHR might be an important factor in the maintenance of hypertension.

Plasma cyclic nucleotide responses to methacholine and epinephrine in patients with migraine.

SYNOPSISThe purpose of the present study is to show anomalies of the plasma cyclic nucleotide responses of patients with migraine to intramuscular injections of methacholine (80 μg/kg body wt) and epinephrine (0.4 mg/person). The methacholine‐ or epinephrine‐induced increases in plasma cyclic GMP were much larger in patients with migraine than in controls. In the case of methacholine injection, there was also a small but significant rise of plasma cyclic AMP in patients with migraine, while no change was observed in controls. On the other hand, there was no significant difference in the epinephrine‐induced increase in plasma cyclic AMP between patients with migraine and controls. From these findings it may be assumed that cholinergic or a‐adrenergic receptor responses are enhanced in patients with migraine.

Anaphylaxis-induced increase in plasma cyclic AMP dependent on endogenous catecholamines in rats.

Plasma cyclic AMP levels during anaphylactic shock in rats was studied in 7 groups of animals: (1) control rats; (2) rats with adrenomedullectomy; (3) rats treated with propranolol; (4) rats with reserpinization; (5) rats with 6-hydroxydopamine-induced chemical sympathectomy; (6) rats treated with hexamethonium, and (7) rats treated with cocaine (catecholamine uptake inhibitor). All experiments were carried out in ovalbumin-sensitized rats. Plasma cyclic AMP showed a rapid increase during anaphylactic shock in control rats. Adrenomedullectomy abolished the anaphylaxis-induced increase in plasma cyclic AMP, while hexamethonium had no effect. Propranolol caused a dose-dependent abolition of the increase. The treatment of rats with reserpine, 6-hydroxydopamine or cocaine partially inhibited the increase in plasma cyclic AMP. The results show that the adrenal medulla is the major source of catecholamines during anaphylactic shock, and that catecholamines in the adrenergic neuronal terminals may be partly responsible for the anaphylaxis-induced increase in plasma cyclic AMP.

Plasma cyclic nucleotides in spontaneously hypertensive rats : Hyper–response to acute hot stress

An acute hot stress caused a sharp increase in plasma cyclic AMP and cyclic GMP in both spontaneously hypertensive rats(SHR) and normotensive Wistar-Kyoto rats(WKY). This hot stress-induced increase in plasma cyclic AMP was observed even after chemical sympathectomy elicited by 6-hydroxydopamine or :epleting the catecholamine stores in adrenergic neurons by tyramine or reserpinization, but was no longer observable after β-adrenergic blockade by propranolol, blockade of autonomic ganglia by hexamethonium, adrenodemedullation or anesthesia by pentobarbital. These results indicate that the initial stimulation of the central nervous system evoked the release of catecholamines from the adrenal medulla which could activate adenylate cyclase via the stimulation of β-adrenoceptors on the cell surface. The increment of plasma cyclic GMP was not influenced by prior blockade of the peripheral autonomic nervous system, but was totally abolished by pentobarbital. The plasma cyclic AMP and cyclic GMP responses were greater in adult SHR than in young SHR and young and matured WKY. The predominant response of plasma cyclic AMP might be due to a greater release of catecholamine from the adrenal medulla in matured SHR. The hyperresponse of plasma cyclic GMP in adult SHR remains to be fully elucidated. In conclusion, the hyperresponse of plasma cyclic nucleotides in SHR might be related to a maintenance mechanism of the hypertensive state rather than a trigger mechanism of the syndrome.

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.

Strain difference in morphine-induced increase in plasma cyclic AMP and cyclic GMP levels in relation to locomotor activity in male mice.

The effects of morphine on plasma cyclic nucleotide levels and on locomotor activity were investigated in four inbred strains of male mice. Morphine increased both cyclic AMP and cyclic GMP levels as well as locomotor activity in C57BL/6N mice. In BALB/cAnN mice, morphine increased plasma cyclic GMP levels and motor activity without changes in plasma cyclic AMP levels. In C3H/HeN mice, morphine increased plasma cyclic GMP levels without changing cyclic AMP levels and motor activity, but neither plasma cyclic nucleotide levels nor motor activity were increased by morphine in DBA/2N mice. Epinephrine and carbachol increased plasma cyclic AMP and cyclic GMP levels, respectively, in both C57BL and DBA mice. These results show that there is a significant strain difference in the effects of morphine on plasma cyclic nucleotide levels as well as motor activity. The major cause of strain difference in the effects of morphine on cyclic nucleotide levels is unlikely to be due to the difference in the regulation of adenylate cyclase linked to adrenoceptors or that of guanylate cyclase connected with cholinoceptors.

The mechanism of the decrease in serum potassium during insulin-induced hypoglycemia (author's transl)

This study was made to investigate the mechanisms of the changes in serum potassium during a period of insulin-induced hypoglycemia. The following experiments were performed: I) A relationship was observed between the amount of insulin dosage and the levels of serum potassium, blood sugar, and plasma cyclic AMP or plasma cyclic GMP in normal controls and rats. In humans, regular insulin (0.025 approximately 0.15 U/kg) was injected intravenously, and blood samples drawn at intervals were used for estimation. Regular insulin (0.1 approximately 1.0 U/kg) was injected into Wistar strain male rats and blood was drawn at intervals. II) A relationship was observed between those items mentioned above in patients with thyroid diseases or diabetes mellitus. They were injected with regular insulin (0.1 U/kg). III) An effect of spironolactone was observed on the levels of the above mentioned items. Regular insulin (0.075 U/kg) was injected into normal controls after the ingestion of spironolactone. IV) An effect of non-selective beta-blocker was observed on the levels of the above mentioned items. Regular insulin (0.1 U/kg) was injected into normal controls and patients with hyperthyroidism after the ingestion of 20 mg of propranolol. The results obtained were as follows: 1) There was a significant logarithmic dose-response relationship between insulin dose and maximum per cent decrease in serum potassium, and maximum per cent increase in plasma cyclic AMP. (p less than 0.02 approximately 0.01) 2) A significant positive correlation was observed between the maximum per cent decrease in serum potassium and the maximum per cent increase in plasma cyclic AMP during the period of insulin-induced hypoglycemia. (p less than 0.001) 3) The changes in serum potassium and plasma cyclic AMP were significantly greater in patients with hyperthyroidism who were possibly in a hyperdynamic beta-adrenergic circulatory state, and these changes were smaller in patients with hypothyroidism than in the normal controls. When their thyroid functions were normalized by the treatment, the changes in serum potassium and plasma cyclic AMP behaved in the same manner as those in the normal controls. 4) Spironolactone had no effect on any change observed in this study. 5) Neither per cent decrease of serum potassium nor per cent increase of cyclic AMP were influenced by propranolol at 15 minutes, but they decreased 30 minutes after the insulin injection. These results may indicate that a decrease of serum potassium levels during the period of insulin-induced hypoglycemia in both the early and late phases is caused by different mechanisms. The change in serum potassium was accompanied by an increase of plasma cyclic AMP, and furthermore this change was inhibited by beta-blocker. It was suggested that beta-adrenoreceptor play a role in a decrease of serum potassium, especially 30 minutes after a injection of insulin.

Development of tolerance to oral salbutamol in the third trimester of pregnancy: a study of circulatory and metabolic effects.

1 The purpose of the study was to investigate whether a development of tolerance does occur or not to salbutamol-induced cardiovascular and metabolic effects after oral long term treatment in pregnancy. 2 Twenty-three women in late pregnancy were given an oral dose of 4 mg salbutamol in the morning after an overnight fast. Ten of the women had not been exposed to beta-adrenoceptor agonists earlier in their pregnancy (group A). Thirteen of the women had been treated with salbutamol in a dose of 4 mg four times a day for 12 to 33 days preceding the study (group B). 3 Blood samples were collected every 30 min for 120 min and analyzed for cyclic AMP, insulin, C-peptide, glucose, lactate, glycerol, non-esterified fatty acids (NEFA) and 3-hydroxybutyrate (3-HB). Heart rate and blood pressure were recorded simultaneously. 4 In group A there was significant increase in plasma cyclic AMP and increased glycogenolysis, lipolysis and insulin secretion. In this group there were also significant cardiovascular effects, that is, an increase of heart rate and decrease of diastolic blood pressure. 5 In group B the effects of salbutamol were significantly less pronounced, indicating a development of tolerance. 6 We conclude that the metabolic side-effects are not sufficient reason to withhold beta-adrenoceptor agonists to healthy pregnant women with threatened premature labour, since tolerance rapidly develops to these actions.

Plasma cyclic amp in the morphine-tolerant rat

Effects of morphine on plasma cyclic AMP leveis in the rat were investigated. Morphine (20 mg kg , s.c. + 4 mg kg/hr , i.v.) produced an increase in plasma cyclic AMP concentrations at 1hr and sustained elevated levels for several hours, but the levels returned to normal levels at 48 hr. the 48 hr increase in plasma cyclic AMP elicited by morphine (20 mg kg , s.c.) was far smaller than that of 1 hr; the plasma concentration of morphine was at the same level as the 1 hr. This indicated the development of tolerance to the morphine induced increase in plasma cyclic AMP. At 48 hr an epinephrine challenge increased plasma cyclic AMP to the same extent as in naive rats. Therefore, desensitization of peripheral tissues as being responsible for the increase in the plasma cyclic AMP could be ruled out. the development of tolerance by the sympatho-adrenal reflex elicited by morphine was suggested. In naioxone-precipitated abstinence, plasma cyclic AMP showed a 4-fold increase but. on spontaneous withdrawal, it showed on a slight but significant increase. It was concluded that plasma cyclic AMP is a sensitive index of tolerance to and dependence on morphine.

Triiodothyronine binding to lymphocyte nuclei and plasma cyclic AMP response to intravenous glucagon in patients with peripheral resistance to thyroid hormones

In vitro studies of nuclear binding of triiodothyronine (T3) in lymphocytes were performed in three members of a family with hereditary peripheral resistance to thyroid hormone action. Ficoll-Hypaque purified lymphocytes were used; the binding characteristics were analyzed by Scatchard's methods. In 5 euthyroid subjects the apparent mean equilibrium association constant (Ka) was 6.2 x 10(9) l/mol and the mean maximal binding capacity (Cap) 14.4 x 10(-15) mol/100 microgram DNA. In the 3 members of the family one single set os saturable T3 nuclear binding sites with affinity constants similar to those in the controls (mean Ka = 3.2 x 10(9) l/mol; mean Cap = 17.4 x 10(-15) mol/100 microgram DNA) were found. The glucagon stimulated increase in plasma cyclic AMP was studied in 6 healthy subjects and the four members of the family. The plasma cyclic AMP levels of the patients with hormone resistance were generally within the normal range. These observations demonstrate that in these patients with peripheral resistance to thyroid hormone binding of T3 to the receptor in the nucleus of lymphocytes is normal; in relation to the high circulating thyroid hormone levels, the thyroid hormone mediated cyclic AMP response is disturbed, suggesting that the defect is at the post-receptor effector level.

Increase in plasma cyclic AMP levels elicited by naloxone in morphine-dependent male mice

Naloxone increased the levels of plasma cyclic AMP in morphine-dependent male mice in which a morphine pellet had been implanted for 72 hr, but not in the nondependent mice. The effect of naloxone on the cyclic AMP levels disappeared 24 hr after the removal of the morphine pellet. Pretreatment with propranolol, hexamethonium or adrenalectomy, but not with atropine or phentolamine inhibited the effect of naloxone. These results suggest that naloxone increases the level of plasma cyclic AMP by releasing catecholamines from the adrenal medulla, thereby activating the adenylate cyclase in the tissues through the stimulation of β-adrenergic receptors. A moderate increase in plasma cyclic AMP was also seen in morphine-dependent mice 1 hr after the removal of the morphine pellet. It is proposed that the increase in the levels of plasma cyclic AMP elicited by naloxone-precipitated or abrupt withdrawal is one of the withdrawal symptoms and probably can be used as a screening method for assessing the degree of physical dependence in laboratory animals.

Abnormal beta adrenergic responsiveness in allergic subjects: Analysis of isoproterenol-induced cardiovascular and plasma cyclic adenosine monophosphate responses

Beta adrenergic responses were compared between normal control subjects and patients with allergic asthma or allergic rhinitis and a group of asymptomatic individuals with positive immediate hypersensitivity skin tests. Two responses to infused isoproterenol were monitored: increases in pulse pressure and plasma cyclic adenosine monophosphate (cyclic AMP). Although the normal control subjects responded with increases in pulse pressure of greater magnitude than the other groups in response to infused isoproterenol, the differences in responsiveness were more apparent when the concentration of isoproterenol required to increase the pulse pressure ≧22 mm Hg was compared. The 25 control subjects required 8.04 ± 0.48 ng/kg/min isoproterenol, whereas the 17 asthmatic patients required 14.25 ± 1.21 (p < 0.0001), the eight subjects with allergic rhinitis required 12.75 ± 1.58 (p < 0.0005), and the seven asymptomatic subjects with positive skin tests needed 11.1 ± 1.26 (p < 0.01). Comparison of baseline plasma cyclic AMP levels of the groups revealed no apparent differences. However, the normal controls responded to isoproterenol with larger increases in plasma cyclic AMP than the other groups at both 6 and 9 ng/kg/min. Furthermore, significantly fewer of the subjects with asthma, rhinitis, or positive skin tests demonstrated an increase in plasma cyclic AMP ≧ 50% above baseline as compared with controls. Thus, as reflected in both cardiovascular and cyclic AMP responses to infused isoproterenol, allergic asthmatic subjects are hyporesponsive as compared with normal controls. However, a comparable degree of diminished responsiveness is seen in subjects with allergic rhinitis or in asymptomatic individuals with positive skin tests. Therefore beta adrenergic hyporesponsiveness appears to be related with the atopic state rather than with asthma.

Effect of narcotic analgesics on plasma cyclic AMP levels in male mice

Systemic administration of morphine, as well as pethidine and pentazocine, increased plasma cyclic AMP levels in male mice. Intracerebroventricular administration of morphine and β-endorphin also increased plasma cyclic AMP levels. The effect of morphine and β-endorphin was antagonized by naloxone indicating the involvement of opiate receptors in the central nervous system for the effect of morphine on cyclic AMP levels. Tolerance was shown to develop to the action of morphine in increasing the plasma cyclic AMP. The morphine-induced increase in plasma cyclic AMP was abolished by treatment with propranolol or pentolinium or by adrenalectomy but not by treatment with atropine, phentolamine, 6-hydroxydopamine or α-methyltyrosine. These findings suggest that morphine increases plasma cyclic AMP levels mainly by releasing catecholamines, from the adrenal medulla, and these activate adenylate cyclase via the stimulation of β-adrenoceptors.

Cyclic AMP metabolism and adenylate cyclase concentration in patients with advanced hepatic cirrhosis

Glucagon was tested for its effect on plasma adenosine 3′,5′-cyclic monophosphate (cyclic AMP), insulin, and glucose in healthy subjects and in patients with advanced cirrhosis of the liver. In the normal subjects, intravenous infusion of glucagon caused a significant increase in plasma cyclic AMP, glucose, and insulin. In advanced cirrhotics, plasma cyclic AMP, glucose, and insulin did not increase. Adenylate cyclase concentration was measured in liver tissue from end stage cirrhotic patients and from brain-dead organ donors whose cardiovascular function was maintained in a stable state. Basal and total adenylate cyclase concentration were not different in the two groups. Adenylate cyclase from the livers of advanced cirrhotics was, however, significantly less responsive to glucagon stimulation than was that from donor livers. Hepatocytes in advanced cirrhosis have abnormal metabolic behavior characterized by abnormal adenylate cyclase-cyclic AMP response to hormonal stimulation.

The plasma cyclic AMP response to catecholamines as potentiated by phentolamine in rats

Norepinephrine failed to increase plasma cyclic AMP when injected alone into fasted rats, in contrast with sharp increases elicited by isoproterenol, epinephrine or tyramine. In rats pretreated with 6-hydroxydopamine or cocaine, however, there was a significant increase in plasma cyclic AMP after norepinephrine injection, suggesting that the rapid neuronal catecholamine uptake was at least partly responsible for the lack of norepinephrine action. Phentolamine was very effective in enhancing the epinephrine-, norepinephrine- or tyramine-induced increase in plasma cyclic AMP but without effect on the isoproterenol-induced increase. Blockade of postsynaptic α-adrenoceptors, rather than of presynaptic receptors, is likely to be involved in the phentolamine potentiation. since it was even observed in rats treated 6-hydroxydopamine or cocaine. A discussion is presented regarding the mechanism by which cyclic AMP generation is influenced by the α- and β-adrenoceptor interaction on effector cell membranes.

Increases in plasma cyclic AMP dependent on endogenous catecholamines

Administration of tyramine (with or without phentolamine) as well as induction of ether anesthesia or insulin hypoglycemia caused a sharp increase in plasma cyclic AMP in rats. Based onthe findings that the treatment of rats with reserpine, 6-hydroxydopamine, cocaine or propranolol totally abolished tyramine-induced increases in plasma cyclic AMP, it was concluded that catecholamines released from sympathetic neuronal terminals by tyramine could activate adenylate cyclase via the stimulation of postsynaptic β-adrenoceptors. In contrast, catecholamines secreted from adrenal medulla were largely responsible for the increase in plasma cyclic AMP induced by ether anesthesia; whereas glucagon, in addition to adrenal catecholamines, played a significant role in hypoglycemia-induced increases in plasma cyclic AMP. Assay of plasma cyclic AMP following these stimuli is very promising as a test for adrenergic activities in experimental and clinical studies.