Effect of lanthanum on the inotropic response of isoproterenol: role of the superficially bound calcium

1985 ◽  
Vol 63 (9) ◽  
pp. 1106-1112 ◽  
Author(s):  
Ahmad B. Fawzi ◽  
John H. McNeill
Keyword(s):  
Cyclic Amp ◽  
Positive Inotropic Effect ◽  
Direct Action ◽  
Maximum Response ◽  
Inotropic Response ◽  
Guinea Pig Heart ◽  
Low Concentrations ◽  
Stimulation Of ◽  
Calcium Pool

Mammalian myocardial contractility is believed to be related to the amount of calcium contained in a highly labile superficial calcium pool. The purpose of this study was to determine the role of such sites in the positive inotropic effect of isoproterenol. Lanthanum, an ion that is restricted to the extracellular space and that displaces the superficially bound calcium, was selected as a tool for this investigation. In Langendorff preparations of the guinea pig heart, lanthanum decreased the basal contractility index (+ dP/dtmax) in a concentration-dependent fashion (0.05–3μM) and blocked the inotropic response of isoproterenol in a noncompetitive manner (0.25–3 μM). Three-micromolar lanthanum (i) reduced basal contractility and the maximum response to isoproterenol by 97 and 95%, respectively, (ii) had no significant effect (p > 0.05) on basal and isoproterenol-induced cyclic AMP levels, and (iii) had no effect on the Kd of [3H]nitrendipine binding, but reduced the Bmax by 31%. While 1 μM lanthanum reduced basal contractility and the maximum response to isoproterenol by 90 and 70%, respectively, it had no effect on [3H]nitrendipine binding. These results suggest that the effects of such low concentrations of lanthanum (≤3 μM) are not related to a direct action on the calcium channels and are not mediated by an inhibition of isoproterenol stimulation of the enzyme adenylate cyclase. Therefore, one interpretation of these results suggests that superficially bound calcium is required for the inotropic response of isoproterenol.

scholarly journals The role of Ca2+ in steroidogenesis in Leydig cells. Stimulation of intracellular free Ca2+ by lutropin (LH), luliberin (LHRH) agonist and cyclic AMP

1986 ◽  
Vol 236 (1) ◽  
pp. 45-51 ◽  
Author(s):  
M H F Sullivan ◽  
B A Cooke
Keyword(s):  
Cyclic Amp ◽  
Leydig Cells ◽  
Second Messenger ◽  
Lhrh Agonist ◽  
Dibutyryl Cyclic Amp ◽  
Testosterone Production ◽  
Agonist Action ◽  
Low Concentrations ◽  
Stimulation Of

The requirements of purified rat Leydig cells for intra- and extra-cellular Ca2+ during steroidogenesis stimulated by LH (lutropin), cyclic AMP analogues and LHRH (luliberin) agonist were investigated. The intracellular Ca2+ concentrations ([Ca2+]i) were measured by using the fluorescent Ca2+ chelator quin-2. The basal [Ca2+]i was found to be 89.4 +/- 16.6 nM (mean +/- S.D., n = 25). LH, 8-bromo cyclic AMP and dibutyryl cyclic AMP increased [Ca2+]i, by 300-500 nM at the highest concentrations of each stimulator, whereas LHRH agonist only increased [Ca2+]i by a maximum of approx. 60 nM. Low concentrations of LH (less than 1 pg/ml) and all concentrations of LHRH agonist increased testosterone without detectable changes in cyclic AMP. With amounts of LH greater than 1 pg/ml, parallel increases in cyclic AMP and [Ca2+]i occurred. The steroidogenic effect of the LHRH agonist was highly dependent on extracellular Ca2+ concentration ([Ca2+]e), whereas LH effects were only decreased by 35% when [Ca2+]e was lowered from 2.5 nM to 1.1 microM. No increase in [Ca2+]i occurred with the LHRH agonist in the low-[Ca2+]e medium, whereas LH (100 ng/ml) gave an increase of 52 nM. It is concluded that [Ca2+]i can be modulated in rat Leydig cells by LH via mechanisms that are both independent of and dependent on cyclic AMP, whereas LHRH-agonist action on [Ca2+]i is independent of cyclic AMP. The evidence obtained suggests that, at sub-maximal rates of testosterone production, Ca2+, rather than cyclic AMP, is the second messenger, whereas for maximum steroidogenesis both Ca2+- and cyclic-AMP-dependent pathways may be involved.

scholarly journals The role of insulin in the modulation of glucagon-dependent control of phenylalanine hydroxylation in isolated liver cells

1987 ◽  
Vol 242 (3) ◽  
pp. 655-660 ◽  
Author(s):  
M J Fisher ◽  
A J Dickson ◽  
C I Pogson
Keyword(s):  
Cyclic Amp ◽  
Insulin Action ◽  
Phenylalanine Hydroxylase ◽  
Liver Cells ◽  
Phosphorylation State ◽  
Isolated Liver Cells ◽  
The Impact ◽  
Isolated Liver ◽  
Stimulation Of

The stimulation of phenylalanine hydroxylation in isolated liver cells by sub-maximally effective concentrations of glucagon (less than 0.1 microM) is antagonized by insulin (0.1 nM-0.1 microM). This phenomenon is a consequence of a decrease in the glucagon-stimulated phosphorylation of phenylalanine hydroxylase from liver cells incubated in the presence of insulin. The impact of insulin on the phosphorylation state and activity of the hydroxylase is mimicked by incubation of liver cells in the presence of orthovanadate (10 microM). A series of cyclic AMP and cyclic GMP analogues enhanced phenylalanine hydroxylation: in each case insulin diminished the stimulation of flux. These results are discussed in the light of the characteristics of insulin action on other metabolic processes.

scholarly journals THE TUMOR-PROMOTER PHORBOL ESTER (12-0-TETRADECANOYL-PHORBOL-13-ACETATE), A POTENT AGGREGATING AGENT FOR BLOOD PLATELETS

1974 ◽  
Vol 60 (2) ◽  
pp. 325-336 ◽  
Author(s):  
Marjorie B. Zucker ◽  
Walter Troll ◽  
Sidney Belman
Keyword(s):  
Platelet Aggregation ◽  
Cyclic Amp ◽  
Phorbol Ester ◽  
Platelet Rich Plasma ◽  
Direct Action ◽  
Blood Platelets ◽  
Tumor Promoter ◽  
Metabolic Inhibitors ◽  
Rapid Phase ◽  
Low Concentrations

The phorbol ester 12-0-tetradecanoyl-phorbol-13-acetate, a potent tumor-promoting agent, caused irreversible platelet aggregation when more than 0.02 µM was stirred with human citrated or heparinized platelet-rich plasma (PRP). With washed platelets, 1 nM was effective. The alcohol phorbol, which has little tumor-promoting activity, failed to cause platelet aggregation. With all but low concentrations of phorbol ester, aggregation was succeeded by a rapid phase. The latter was prevented or reduced by enzymes which destroy ADP and by aspirin, was associated with a change in platelet shape, and was presumably due to released ADP. At higher concentrations, only a rapid phase was seen, and these inhibitors were not effective. Low concentrations did not aggregate platelets in PRP containing sufficient EDTA or EGTA to chelate ionized calcium or in PRP from thrombasthenic patients; higher concentrations caused slight aggregation. Both the primary, non-ADP-dependent aggregation and the rapid ADP-dependent aggregation were markedly inhibited by substances which increase cyclic AMP, metabolic inhibitors, and the sulfhydryl inhibitor N-ethylmaleimide. Phorbol ester reduced platelet cyclic AMP only when it had been previously elevated by prostaglandin E1. 1 µM did not release ß-glucuronidase, lactic dehydrogenase, or inflammatory material from platelets in 4–5 min despite marked aggregation, but liberated all three in 30 min. The possibility is discussed that low phorbol ester concentrations cause primary aggregation by a direct action on platelet actomyosin.

Possible role of cyclic GMP in stimulus-secretion coupling by salt gland of the duck

1979 ◽  
Vol 237 (5) ◽  
pp. C200-C204 ◽  
Author(s):  
D. J. Stewart ◽  
J. Sax ◽  
R. Funk ◽  
A. K. Sen
Keyword(s):  
Cyclic Amp ◽  
Guanylate Cyclase ◽  
Cyclic Gmp ◽  
Salt Gland ◽  
Domestic Ducks ◽  
Stimulus Secretion Coupling ◽  
Stimulation Of

Stimulation of salt galnd secretion in domestic ducks in vivo increased the cyclic GMP concentration of the tissue, but had no effect on cyclic AMP levels. Methacholine, which is known to stimulate sodium transport by the glands both in vivo and in vitro, stimulated ouabain-sensitive respiration in salt gland slices. Cyclic GMP stimulated ouabain-sensitive respiration to the same extent as methacholine. Guanylate cyclase stimulators, hydroxylamine and sodium azide, also stimulated ouabain-sensitive respiration. The stimulation of ouabain-sensitive respiration by methacholine was blocked either by atropine or by removal of calcium from the incubation medium. The stimulation of ouabain-sensitive respiration by cyclic GMP still occurred in the absence of calcium. The above observations seem to indicate that cyclic GMP acts as a tertiary link in the process of stimulus-secretion coupling in the tissue.

THE EFFECT OF ANGIOTENSIN ON RAT INTESTINAL FLUID TRANSFER

1970 ◽  
Vol 48 (1) ◽  
pp. 39-NP ◽  
Author(s):  
N. T. DAVIES ◽  
K. A. MUNDAY ◽  
B. J. PARSONS
Keyword(s):  
Fluid Transport ◽  
Direct Action ◽  
Rat Jejunum ◽  
Intestinal Fluid ◽  
Low Concentrations ◽  
Fluid Transfer ◽  
High Concentrations ◽  
Dose Dependent ◽  
Everted Sacs

SUMMARY Fluid transfer by isolated everted sacs of rat jejunum, ileum and intact colon prepared from adrenalectomized-nephrectomized rats 48 h after operation was reduced when compared with that of sacs prepared from untreated controls (P < 0·001). Angiotensin at 10−10 g/ml significantly (P < 0·01) stimulated fluid transfer by intestinal sacs prepared from the adrenalectomized-nephrectomized rats; all three regions of gut were equally sensitive. Fluid transfer was similarly reduced in stripped colon sacs prepared from adrenalectomized-nephrectomized rats. Angiotensin had a dose-dependent biphasic action on fluid transfer by stripped colon sacs: low concentrations (10−11 and 10−12 g/ml) stimulated (P < 0·05), whilst high concentrations (10−9 and 10−8 g/ml) inhibited fluid transfer (P < 0·01). Histological examination of the colon preparations showed that the stripping procedure removed the ganglia, indicating that both angiotensin effects were due to direct action on the colon mucosa. The significance of these results is discussed in relation to the role of angiotensin in the control of salt and fluid transport by the mammalian kidney and other epithelial tissues.

scholarly journals Role of Protein Phosphatases in Cyclic AMP-mediated Stimulation of Hepatic Na+/Taurocholate Cotransport

1998 ◽  
Vol 273 (45) ◽  
pp. 30039-30045 ◽  
Author(s):  
Sunil Mukhopadhyay ◽  
Cynthia R. L. Webster ◽  
M. Sawkat Anwer
Keyword(s):  
Cyclic Amp ◽  
Protein Phosphatases ◽  
Stimulation Of

scholarly journals Adenosine 3':5'-monophosphate content and actions in the division cycle of synchronized HeLa cells.

1976 ◽  
Vol 71 (2) ◽  
pp. 515-534 ◽  
Author(s):  
C E Zeilig ◽  
R A Johnson ◽  
E W Sutherland ◽  
D L Friedman
Keyword(s):  
Cell Cycle ◽  
Cyclic Amp ◽  
Hela Cells ◽  
S Phase ◽  
Intracellular Camp ◽  
Specific Effects ◽  
Low Concentrations ◽  
High Concentrations ◽  
Camp Levels ◽  
Stimulation Of

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.

Transepithelial Potential Changes During Stimulation of Isolated Salivary Glands with 5-Hydroxytryptamine and Cyclic Amp

1972 ◽  
Vol 56 (1) ◽  
pp. 139-153
Author(s):  
MICHAEL J. BERRIDGE ◽  
WILLIAM T. PRINCE
Keyword(s):  
Cyclic Amp ◽  
Salivary Glands ◽  
Electrical Response ◽  
Cation Transport ◽  
Anion Transport ◽  
Adenyl Cyclase ◽  
Positive Potential ◽  
Dose Dependent ◽  
Stimulation Of

1. The role of cyclic AMP in mediating the action of 5-HT on salivary glands has been studied by measuring transepithelial potentials. 2. The lumen of unstimulated glands is 4 mV positive but becomes 12 mV negative after treatment with 5-HT (10-8M). Both the potential and the secretory responses to 5-HT are dose-dependent over the same concentration range. 3. The electrical response of salivary glands to cyclic AMP is qualitatively different to that of 5-HT; instead of going negative the potential goes more positive. 4. An increase in positive potential is also observed after treatment with theophylline (10-2M), or when glands are stimulated with 5-HT in a chloride-free saline. 5. These results are consistent with the idea that 5-HT has two actions. One is to stimulate the enzyme adenyl cyclase to synthesize cyclic AMP, which, in turn, stimulates cation transport. The other is to increase anion transport by a mechanism which is independent of cyclic AMP.

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