Longitudinal Studies of Platelet Cyclic AMP during Healthy Pregnancy and Pregnancies at Risk of Pre-Eclampsia

1995 ◽  
Vol 89 (1) ◽  
pp. 91-99 ◽  
Author(s):  
E. H. Horn ◽  
J. A. Cooper ◽  
E. Hardy ◽  
S. Heptinstall ◽  
P. C. Rubin
Keyword(s):  
At Risk ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Previous History ◽  
Phosphodiesterase Inhibitor ◽  
Surface Receptors ◽  
Healthy Pregnancy ◽  
Cyclic Amp Accumulation ◽  
History Of

1. Platelet behaviour in vitro in relation to cyclic AMP was studied longitudinally during pregnancy and in the same women when they were not pregnant. Subjects comprised a group of healthy primigravidae and a group of women deemed at risk of pre-eclampsia, on the basis of a previous history of the condition. 2. There was a progressive decline during pregnancy in sensitivity of platelets to inhibition of the arachidonic acid-induced release reaction by agents which act via cyclic AMP. This effect was maximum at 36 weeks' gestation. 3. Basal platelet cyclic AMP levels, and those in the presence of a phosphodiesterase inhibitor, did not change throughout the period of the study. 4. By contrast, platelet cyclic AMP accumulation in response to a variety of adenylate cyclase stimulators was reduced from early pregnancy, throughout the gestational period, compared with post-natally. This effect was noted when platelets were incubated with prostaglandins acting via different surface receptors or with forskolin and was most marked on co-incubation with a phosphodiesterase inhibitor. 5. Compared with healthy women, platelets from women with a previous history of pre-eclampsia tended to accumulate less cyclic AMP in response to adenylate cyclase stimulators. This was the case both during pregnancy and post-natally. Further investigation of adenylate cyclase activity in platelets in relation to pre-eclampsia is required.

scholarly journals Use of forskolin to study the relationship between cyclic AMP formation and bone resorption in vitro

1986 ◽  
Vol 240 (2) ◽  
pp. 529-539 ◽  
Author(s):  
U H Lerner ◽  
B B Fredholm ◽  
M Ransjö
Keyword(s):  
Bone Resorption ◽  
Cyclic Amp ◽  
Phosphodiesterase Inhibitor ◽  
Inhibitory Effect ◽  
Cyclic Amp Accumulation ◽  
The Relationship ◽  
Dose Dependent ◽  
Old Mice ◽  
45Ca Release

The effect of the adenylate cyclase activator forskolin on bone resorption and cyclic AMP accumulation was studied in an organ-culture system by using calvarial bones from 6-7-day-old mice. Forskolin caused a rapid and fully reversible increase of cyclic AMP, which was maximal after 20-30 min. The phosphodiesterase inhibitor rolipram (30 mumol/l), enhanced the cyclic AMP response to forskolin (50 mumol/l) from a net cyclic AMP response of 1234 +/- 154 pmol/bone to 2854 +/- 193 pmol/bone (mean +/- S.E.M., n = 4). The cyclic AMP level in bones treated with forskolin (30 mumol/l) was significantly increased after 24 h of culture. Forskolin, at and above 0.3 mumol/l, in the absence and the presence of rolipram (30 mumol/l), caused a dose-dependent cyclic AMP accumulation with an calculated EC50 (concentration producing half-maximal stimulation) value at 8.3 mumol/l. In 24 h cultures forskolin inhibited spontaneous and PTH (parathyroid hormone)-stimulated 45Ca release with calculated IC50 (concentration producing half-maximal inhibition) values at 1.6 and 0.6 mumol/l respectively. Forskolin significantly inhibited the release of 3H from [3H]proline-labelled bones stimulated by PTH (10 nmol/l). The inhibitory effect by forskolin on PTH-stimulated 45Ca release was significant already after 3 h of culture. In 24 h cultures forskolin (3 mumol/l) significantly inhibited 45Ca release also from bones stimulated by prostaglandin E2 (1 mumol/l) and 1 alpha-hydroxycholecalciferol (0.1 mumol/l). The inhibitory effect of forskolin on spontaneous and PTH-stimulated 45Ca release was transient. A dose-dependent stimulation of basal 45Ca release was seen in 120 h cultures, at and above 3 nmol of forskolin/l, with a calculated EC50 value at 16 nmol/l. The stimulatory effect of forskolin (1 mumol/l) could be inhibited by calcitonin (0.1 unit/ml), but was insensitive to indomethacin (1 mumol/l). Forskolin increased the release of 3H from [3H]proline-labelled bones cultured for 120 h and decreased the amount of hydroxyproline in bones after culture. Forskolin inhibited PTH-stimulated release of Ca2+, Pi, beta-glucuronidase and beta-N-acetylglucosaminidase in 24 h cultures. In 120 h cultures forskolin stimulated the basal release of minerals and lysosomal enzymes.(ABSTRACT TRUNCATED AT 400 WORDS)

Renal cyclic AMP accumulation and adenulate cyclase stimulation by erythropoietic agents

1975 ◽  
Vol 229 (5) ◽  
pp. 1387-1392 ◽  
Author(s):  
GM Rodgers ◽  
JW Fisher ◽  
WJ George
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Regional Distribution ◽  
Renal Medulla ◽  
Iron Incorporation ◽  
Erythropoietin Production ◽  
Cyclic Amp Accumulation ◽  
Stimulation Of

The regional distribution of cyclic AMP in the kidney was determined following erythropoietic stimulation with hypoxia and cobalt. Following these stimuli, increases in renal cyclic AMP concentrations were restricted to the cortex. The basis for this localization in the case of cobalt treatment was found to reside in the stimulation of renal cortical adenylate cyclase activity in vitro by concentrations of cobalt similar to those found in vivo. The level of cobalt in the cortex after cobalt treatment was found to approach 500 mumol/kg of tissue, whereas no detectable levels of cobalt were found in the renal medulla. Additionally, other agents such as parathyroid hormone and lactic acid, that are known to lack stimulatory effects on medullary adenylate cyclase, were found to stimulate the cortical enzyme. This stimulation of renal cortical adenylate cyclase correlates with enhanced erythropoiesis as demonstrated by increased radiolabeled iron incorporation into erythrocytes. These results support previous reports which suggest that renal cortical cyclic AMP mediates erythropoietin production in response to erythropoietically active agents.

Calmodulin regulation of cellular cyclic AMP production in response to arginine vasopressin, prostaglandin E2 and forskolin in rat renal papillary collecting tubule cells in culture

1985 ◽  
Vol 107 (1) ◽  
pp. 15-22 ◽  
Author(s):  
S. Ishikawa ◽  
T. Saito ◽  
T. Kuzuya
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Arginine Vasopressin ◽  
Phosphodiesterase Inhibitor ◽  
Prostaglandin E ◽  
Cyclic Amp Accumulation ◽  
Collecting Tubule ◽  
Tubule Cells ◽  
A Site ◽  
Cellular Ca

ABSTRACT The effect of calmodulin on the stimulation of cyclic AMP production by arginine vasopressin (AVP), prostaglandin E2 (PGE2) and forskolin was examined in cultured renal papillary collecting tubule cells of the rat. In the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine submaximal concentrations of AVP (1 nmol/l), PGE2 (20 nmol/l) and forskolin (240 nmol/l) significantly increased cellular cyclic AMP accumulation by 2·3-, 6·0- and 8·4-fold respectively. Two chemically dissimilar inhibitors of calmodulin, namely trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7), attenuated the AVP-, PGE2- and forskolin-stimulated cellular production of cyclic AMP in a dose-related manner. Cellular production of cyclic AMP was inhibited by 50% (ID50) by doses ranging from 16 to 28 μmol trifluoperazine/1 and 35 to 44 μmol W-7/1. Basal accumulation of cellular cyclic AMP was also decreased by treatment with either trifluoperazine or W-7, but the effective dose was higher than that which inhibited cellular cyclic AMP production stimulated by AVP, PGE2 and forskolin. Since forskolin directly activates adenylate cyclase at a site of the catalytic unit and the cellular action of AVP to activate adenylate cyclase is mediated through receptor-guanine nucleotide regulatory-catalytic units, the present study indicates calmodulin regulation of basal, AVP-, PGE2-and forskolin-activated adenylate cyclase in the papillary collecting tubule cells. The inhibition of AVP- or PGE2-induced cellular cyclic AMP production by treatment with either Ca2+-free medium or verapamil, a blocker of cellular Ca2+ uptake, was demonstrated and suggests that an increase in cytosol Ca2+, which interacts with calmodulin to form an active complex is, at least in part, due to the increased cellular influx of Ca2+ from the extracellular space. J. Endocr. (1985) 107, 15–22

The human eccrine sweat gland adenylate cyclase system: response to agonists

1985 ◽  
Vol 68 (4) ◽  
pp. 433-439 ◽  
Author(s):  
A. K. Khullar ◽  
V. Schwarz ◽  
P. D. Wilson
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Cyclic Gmp ◽  
Sweat Gland ◽  
Sweat Glands ◽  
System Response ◽  
Renal Tubules ◽  
Adenylate Cyclase System ◽  
Cyclic Amp Accumulation

1. Cyclic AMP accumulation has been measured in whole human sweat glands. The mean rate in glands from 19 subjects was 0.519 ± 0.316 pmol of cyclic AMP formed 5 min−1 μg−1 of DNA, which is comparable with that reported for other tissues. 2. Cyclic AMP accumulation in the sweat gland is stimulated fourfold by prostaglandin (PG) E1 and fivefold by PGE2 (0.1 mmol/l), in accord with stimulation in renal tubules and medullary membranes. 3. Bradykinin (10 μg/ml) increases the rate threefold and this is substantially prevented by indomethacin (1.5 × 10−5 mol/l), as also is a five-fold stimulation by cyclic GMP (10−5 mol/l). 4. Mecholyl (10−2 mol/l) and isoprenaline (6 × 10−6 mol/l) increase the rate five- and four-fold respectively, and these agonist effects are largely abolished by atropine and propranolol. 5. The stimulation and inhibition pattern suggests a direct action of PGE, enhancement of prostaglandin synthetase by cyclic GMP and stimulation of guanylate cyclase by mecholyl and bradykinin. Isoprenaline presumably stimulates adenylate cyclase directly. 6. This complex chain of events, from cholinergic stimulation to an enhancement of adenylate cyclase, demonstrated in vitro, constitutes a potential for flexible and fine control of sweat gland function.

Cytochemical Evidence for Presynatic β-Adrenergic Regulation of Secretion in the Developing Rat Submandibular Gland

1977 ◽  
Vol 35 ◽  
pp. 430-431
Author(s):  
L.S. Cutler
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Submandibular Gland ◽  
Neonatal Rat ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Parotid Glands ◽  
Adrenergic Agonist ◽  
Rat Submandibular Gland

Many studies previously have shown that the B-adrenergic agonist isoproterenol and the a-adrenergic agonist norepinephrine will stimulate secretion by the adult rat submandibular (SMG) and parotid glands. Recent data from several laboratories indicates that adrenergic agonists bind to specific receptors on the secretory cell surface and stimulate membrane associated adenylate cyclase activity which generates cyclic AMP. The production of cyclic AMP apparently initiates a cascade of events which culminates in exocytosis. During recent studies in our laboratory it was observed that the adenylate cyclase activity in plasma membrane fractions derived from the prenatal and early neonatal rat submandibular gland was retractile to stimulation by isoproterenol but was stimulated by norepinephrine. In addition, in vitro secretion studies indicated that these prenatal and neonatal glands would not secrete peroxidase in response to isoproterenol but would secrete in response to norepinephrine. In contrast to these in vitro observations, it has been shown that the injection of isoproterenol into the living newborn rat results in secretion of peroxidase by the SMG (1).

Induction And Potentiation Of Platelet Aggregation By Clonidine And 7ρ-Aminoclonidine, Partial Agonists Of The α2-Receptor Which Regulates Platelet Adenylate Cyclase

1981 ◽  
Author(s):  
David C Stump ◽  
Donald E Macfarlane
Keyword(s):  
Platelet Aggregation ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Specific Binding ◽  
Phase 1 ◽  
Intrinsic Activity ◽  
Second Phase ◽  
Adrenergic Agents ◽  
Cyclic Amp Accumulation ◽  
Induced Aggregation

Epinephrine induces platelet aggregation, potentiates aggregation by other agents, and blocks the stimulation of the adenylate cyclase by prostaglandins. Synthetic α-adrenergic agents have not been shown to induce aggregation. The effects of clonidine, an α2-agonist, and ρ-aminoclonidine on platelets were examined. Clonidine potentiated aggregation induced by 0.5μM ADP by 1.4-fold (1/2 max 0.5μM). It did not induce significant aggregation itself, and it inhibited aggregation induced by 5μM epinephrine (1/2 max lμM). It inhibited cyclic AMP accumulation induced by PGE1 by a maximum of 25% (1/2 max O.lμM) and it blocked inhibition by epinephrine. No significant specific binding of [3H] clonidine was observed to intact platelets. ρ-Aminoclonidine induced aggregation with delayed second phase (1/2 max 0.2μM), and potentiated ADP aggregation by 2-fold (1/2 max 0.2μM). Aggregation induced by epinephrine was more rapid, and was partially inhibited by ρ-aminoclonidine. It inhibited cyclic AMP accumulation by 50% max (1/2 max O.lμM) and attenuated epinephrine’s effect to the same level. The direct effects of ρ-aminoclonidine were blocked by lμM yohimbine, a selective α2-antagonist. Both clonidine and ρ—aminoclonidine blocked the specific binding of [3H]yohimbine (1/2 max 0.5μM). These results suggest that the platelet bears an α2-receptor with affinity for epinephrine, ρ-aminoclonidine and clonidine as agonists but that these agents display differing intrinsic activity and/or receptor reserve.

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