Accumulation of Adenosine 3′,5′-Monophosphate and Relaxation in the Rat Uterus In Vitro

1971 ◽  
Vol 49 (11) ◽  
pp. 999-1004 ◽  
Author(s):  
Ivo Polacek ◽  
Jean Bolan ◽  
Edwin E. Daniel

Theophylline, diazoxide, and papaverine in low concentrations relaxed the uterus with minimal or no elevation of cyclic AMP (cAMP) levels. In higher concentrations, theophylline relaxed the uterus and increased its cAMP levels, but imidazole reversed the increase in cAMP without causing recontraction. Imidazole and NaF caused uterine contractures but did not detectably decrease cAMP levels until several minutes after the onset of contractures. The uterine relaxations produced by theophylline and/or dibutyryl cAMP in amounts which increased uterine cAMP were not reversed by propranolol. These results eliminate the possibility that propranolol interfered with a relaxant action of cAMP. Along with previous data, these results also show that uterine contractile activity was not determined primarily by the general levels of cAMP and that phosphodiesterase activity in the uterus was insufficient to rapidly affect these cAMP levels. Also, substances like theophylline, diazoxide, and papaverine, postulated to inhibit phosphodiesterase activity, did not bring about their relaxant effects by this mechanism.

1989 ◽  
Vol 61 (02) ◽  
pp. 254-258 ◽  
Author(s):  
Margaret L Rand ◽  
Peter L Gross ◽  
Donna M Jakowec ◽  
Marian A Packham ◽  
J Fraser Mustard

SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.


Author(s):  
Shakiru A. Salami ◽  
Hussein M. Salahdeen ◽  
Abidemi E. Obafemi ◽  
Babatunde A. Murtala

Abstract Objectives Stress responses vary throughout pregnancy and impact of late gestational variable stress (LGVS) with vitamin C supplementation on uterine contractility is barely explored. This study investigates fetal weight outcome and in-vitro uterine contractile responses to pharmacological agents during LGVS exposure. Methods Twenty four nulliparous pregnant rats were divided into four groups of six. During gestation days 10–19, groups 1 & 2 received normal saline and vitamin C (10 mg/kg) respectively. Groups 3 and 4 were exposed to stress (sleep deprivation, predator exposure, immobility, rapid cage changes, noise, and foreign object) with group 4 concurrently supplemented with vitamin C (10 mg/kg). Serum cortisol, oxidative bio-markers, fetal weights and in-vitro contractile responses of excised uterine tissue to acetylcholine (Ach), oxytocin, calcium chloride (CaCl2), potassium chloride (KCl), diclofenac, and magnesium ions were determined. Results Malondialdehyde activity and cortisol were significantly increased in variable stress only exposed group when compared with control and vitamin C supplemented groups. Fetal body weights, superoxide dismutase and catalase activity were significantly reduced in variable stress only exposed group. Significantly impaired contractile responses to Ach, CaCl2 & KCl in variable stress only exposed group were modulated in vitamin C supplemented groups. Impaired contractile response to oxytocin was however not reversed. Relaxation responses to diclofenac and magnesium ions were statistically unaltered across groups. Conclusions Impaired fetal weights and uterine contractile activity to Ach, CaCl2 and KCl during LGVS was modulated by vitamin C supplementation. Impaired oxytocin contractile activity was however unreversed.


1990 ◽  
Vol 68 (4) ◽  
pp. 1017-1023 ◽  
Author(s):  
S. E. Mills ◽  
C. Y. Liu

Abstract The sensitivities of lipolysis and fatty acid synthesis to dibutyryl-cAMP (dbcAMP), epinephrine, ractopamine and clenbuterol were quantified in vitro using porcine adipocytes. Insulin-stimulated lipogenesis showed a biphasic response to dbcAMP, with increased rates at low concentrations and decreased (55%) rates at higher concentrations of dbcAMP. In the absence of insulin, lipogenesis was inhibited 78% by dbcAMP. In the presence of adenosine deaminase or theophylline, all three β-adrenergic agonists inhibited basal lipogenesis, but only epinephrine and ractopamine inhibited insulin-stimulated lipogenesis. The relationship between suppressed lipogenesis and enhanced lipolysis in response to dbcAMP and the β-agonists revealed that 1) basal lipogenesis was more sensitive to inhibition than was the stimulation of lipolysis, 2) sensitivity differences were magnified if adenosine deaminase was present and 3) insulin decreased adipocyte sensitivity to the inhibitory effects of dbcAMP and the β-adrenergic agonists. These results indicate that the relative sensitivities of lipogenesis and lipolysis to β-adrenergic stimulation can be modified by adenosine and insulin. Furthermore, adenosine and insulin antagonize β-adrenergic responses, in part, by cAMP-independent mechanisms.


1977 ◽  
Author(s):  
D.H. Cowan ◽  
M. Kikta ◽  
D. Baunach

Studies of cAMP in human platelets exposed to ethanol were done to assess one possible mechanism for ethanol-related platelet dysfunction. Ingestion of ethanol by 3 subjects produced blood ethanol levels from 65-76 mM. Thrombocytopenia occurred in 1 subject and impaired platelet function occurred in all. Platelet cAMP decreased 36,51, and 59% below control levels. Infusion of ethanol to 2 normals produced blood ethanol levels of 43 mM and decreased platelet cAMP by 15% and 22%. Incubation of normal platelets with 86 mM ethanol in vitro decreased cAMP from 13.8 ± 2.9 (1 SD) to 9.4 ± 3.5 (p<0.02). By contrast, ethanol did not impair the increase in cAMP that occurred with 1.3 μM PGE1. Further, ethanol enhanced the increase in cAMP produced by 2.0 mM papaverine (Pap) by 160-220% and that produced by Pap + PGE1 by 58%. Dopamine, 0.1 mM, caused a 23% decrease in the basal level of cAMP, a 31% decrease below the subnormal level of cAMP seen with ethanol alone, and a 41% reduction in the increased level of cAMP produced by Pap + ethanol. The effect of ethanol on platelet cAMP metabolism is complex. Ethanol reduces basal levels of cAMP, does not decrease elevated levels that result from PGE1 stimulation of adenylate cyclase, and augments the inhibitory effect of Pap on platelet phosphodiesterase (PDE). Despite causing a decrease in basal cAMP levels, ethanol may impair platelet function by potentiating the effect of agents or other conditions which increase cAMP. The effect of ethanol on Pap-stimulated PDE activity may be blocked by dopamine, a neuropharmacologic agent that is actively accumulated by platelets.


1976 ◽  
Vol 71 (2) ◽  
pp. 515-534 ◽  
Author(s):  
C E Zeilig ◽  
R A Johnson ◽  
E W Sutherland ◽  
D L Friedman

The involvement of adenosine 3':5'-monophosphate (cAMP) in the regulation of the cell cycle was studied by determining intracellular fluctuations in cAMP levels in synchronized HeLa cells and by testing the effects of experimentally altered levels on cell cycle traverse. Cyclic AMP levels were lowest during mitosis and were highest during late G-1 or early S phase. These findings were supported by results obtained when cells were accumulated at these points with Colcemid or high levels of thymidine. Additional fluctuations in cAMP levels were observed during S phase. Two specific effects of cAMP on cell cycle traverse were found. Elevation of cAMP levels in S phase or G-2 caused arrest of cells in G-2 for as long as 10 h and lengthened M. However, once cells reached metaphase, elevation of cAMP accelerated the completion of mitosis. Stimulation of mitosis was also observed after addition of CaCl2. The specificity of the effects of cAMP was verified by demonstrating that: (a) intracellular cAMP was increased after exposure to methylisobutylxanthine (MIX) before any observed effects on cycle traverse; (b) submaximal concentrations of MIX potentiated the effects of isoproterenol; and (c) effects of MIX and isoproterenol were mimicked by 8-Br-cAMP. MIX at high concentrations inhibited G-1 traverse, but this effect did not appear to be mediated by cAMP. Isoproterenol slightly stimulated G-1 traverse and partially prevented the MIX-induced delay. Moreover, low concentrations of 8-Br-cAMP (0.10-100 muM) stimulated G-1 traverse, whereas high concentrations (1 mM) inhibited. Both of these effects were also observed with the control, Br-5'-AMP, at 10-fold lower concentrations.


1983 ◽  
Vol 50 (04) ◽  
pp. 831-834 ◽  
Author(s):  
Knut Dalaker ◽  
Hans Prydz

SummaryMouse placental cells are probably constitutive producers of the thromboplastin apoprotein in vitro. The effect of cyclic AMP- elevating compounds on their expression of thromboplastin activity has been studied. Dibutyryl cyclic AMP, the phosphodiesterase inhibitor Ro 20-1724 and the adenyl cyclase stimulator forskolin all decrease the synthesis of thromboplastin. Prostaglandin E2 and the phosphodiesterase inhibitor butyl-methyl-xanthine have a biphasic dose dependent effect. A stimulation was observed at low concentrations, whereas higher doses decreased the synthesis of thromboplastin. Adrenaline had no effect. Combination of two compounds, each at maximally inhibiting concentration gave no significant additive inhibitory effect, showing that they probably act via the same pathway.


1996 ◽  
Vol 74 (5) ◽  
pp. 669-674 ◽  
Author(s):  
Bijay S. Jaiswal ◽  
Gopal C. Majumder

The concentrations of cAMP, cAMP phosphodiesterase (PDE) activity, and the effect of theophylline in vitro on the forward motility (FM) of maturing goat epididymal sperm have been analyzed. cAMP levels increased slowly during transit of the cells from the caput to the proximal cauda, although they acquired a minimal degree of forward progression. The last phase of sperm transit (proximal to distal cauda) was associated with a concomitant sharp rise in the level of both c AMP as well as flagellar motility. PDE activity progressively decreased (approximately threefold) during epididymal maturation, being minimal in mature cauda sperm. Theophylline (30 mM), a specific inhibitor of PDE, markedly activated (10-fold or greater) motility of the sperm derived from proximal-corpus, mid-corpus, distal-corpus, and proximal-cauda epididymides. FM of the native mature caudal sperm was similar to that of the theophylline-treated proximal-cauda sperm. The terminal stage of sperm maturity (proximal to distal cauda) was associated with a markedly reduced level of theophylline-dependent motility activation (approximately 50%). The data are consistent with the view that PDE plays an important role in the initiation of motility during epididymal sperm maturation.Key words: epididymal sperm, cyclic AMP, cyclic AMP phosphodiesterase, flagellar motility, theophylline


1976 ◽  
Vol 156 (2) ◽  
pp. 461-463 ◽  
Author(s):  
C Berne ◽  
A Andersson

It has been suggested that the stimulatory effect of glucose on insulin release may be mediated by the adenylate cyclase-cyclic AMP phosphodiesterase system. In this study it was found that exposure of isolated pancreatic islets to an elevated extracellular glucose concentration for 1 week in vitro caused an increase of the cyclic AMP phosphodiesterase activity in the islet cells. These and previous data indicate that there is an increased turnover of cyclic AMP in B-cells exposed for a prolonged time to a high extracellular glucose concentration, which also causes an increased turnover rate of insulin.


1980 ◽  
Vol 87 (1) ◽  
pp. 153-159 ◽  
Author(s):  
D. G. JUDSON ◽  
SARAH PAY ◽  
K. D. BHOOLA

Porcine relaxin produced a rapid, dose-related rise of cyclic AMP values in rat uterine tissue incubated in vitro. In time-course experiments, peak cyclic AMP concentrations were observed in the uterine slices at 5 min; subsequently the values fell, at first rapidly and then more slowly with the tissue concentration remaining significantly raised at 15 min. Levels of cyclic GMP in the same tissue slices were not significantly altered by relaxin. Furthermore, no increase in basal cyclic AMP values was measured in control slices prepared from the rat heart or jejunum. An increase in cyclic AMP concentration comparable to that found in the rat uterus was observed in slices of porcine uterus and cervix but not of vagina when they were stimulated with porcine relaxin. Our results suggest that the hormonal action of relaxin on the uterus and cervix is mediated through receptors linked to the enzyme, adenylate cyclase.


1976 ◽  
Vol 231 (1) ◽  
pp. 52-55 ◽  
Author(s):  
R Batt ◽  
JM McKenzie

With the use of microelectrodes, membrane potential (MP) was measured in mouse thyroid glands in vitro. A basal resting MP of about -39 mV was confirmed. The initial effect of feeding a low-iodine diet (6-12 days) was hyperpolarization, up to -47 m V; chronic low-iodine diet led to depolarization. Low concentrations of thyrotropin (less than 3 mU/ml superfusate) caused hyperpolarization and high ones (greater than 10 mU/ml) led to depolarization. Cyclic AMP (10(-3) M), dibutyryl cyclic AMP (1.2 X 10(-4) M or 1.2 X 10(-3) M) and theophylline (10(-2) or 10(-3) M) caused similar hyperpolarization: D- and DL-propranolol (5 X 10(-5) -5 X 10(-4) M) produced depolarization and inhibited hyperpolarization by thyrotropin. Conclusions are that hyperpolarization is a consequence of short-term increased secretion of thyrotropin in vivo or of low (near physiological) concentrations in vitro; these effects are probably mediated by cyclic AMP. The relationship to and mechanism of depolarization resulting from chronic enhanced endogenous secretion or high in vitro concentrations of thyrotropin are unknown.


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