scholarly journals Sphingosine-1-phosphate, a putative second messenger, mobilizes calcium from internal stores via an inositol trisphosphate-independent pathway.

1994 ◽  
Vol 269 (5) ◽  
pp. 3181-3188
Author(s):  
M. Mattie ◽  
G. Brooker ◽  
S. Spiegel
Keyword(s):  
Inositol Trisphosphate ◽  
Second Messenger ◽  
Sphingosine 1 Phosphate

Sphingosine-1-Phosphate: A Lipid Second Messenger Regulating Cell Growth and Survival

1998 ◽  
Vol 8 (2) ◽  
pp. 135-145 ◽  
Author(s):  
James R. Van Brooklyn ◽  
Olivier Cuvillier ◽  
Ana Olivera ◽  
Sarah Spiegel
Keyword(s):  
Cell Growth ◽  
Second Messenger ◽  
Growth And Survival ◽  
Sphingosine 1 Phosphate ◽  
Cell Growth And Survival

scholarly journals Ontogeny and Effects of Hypothalamic Pituitary Disconnection on Formation of Inositol Trisphosphate in Fetal Sheep Pituitary Cells

Endocrinology ◽  
2007 ◽  
Vol 148 (3) ◽  
pp. 1440-1444 ◽  
Author(s):  
Luke C. Carey ◽  
Stephen B. Tatter ◽  
James C. Rose
Keyword(s):  
Gestational Age ◽  
Plasma Cortisol ◽  
Inositol Trisphosphate ◽  
Second Messenger ◽  
Late Gestation ◽  
Pituitary Cells ◽  
Fetal Sheep ◽  
The Impact ◽  
Pituitary Adrenal Axis ◽  
Sheep Fetus

In late gestation fetal sheep, the pituitary becomes increasingly responsive to stimulation by arginine vasopressin (AVP). This change appears to be one important factor mediating the plasma cortisol surge, a critical developmental event. It is not known precisely why pituitary corticotropes become more responsive at this time. In this study we examined the possibility that changes in second messenger generation [inositol trisphosphate (IP3)] are responsible. Two studies were undertaken. The first was an ontogeny study, where pituitaries were isolated from 100-, 120-, and 140-d gestational age (dGA) fetal sheep. Cells were cultured, stimulated with AVP, and the formation of IP3 assessed. The amount of IP3 generated increased with gestational age (percent increases from unstimulated controls were 4.6, 11.5, and 21.5 for 100, 120, and 140 dGA, respectively), with significant differences between the 140-dGA group and both earlier groups apparent. The second study examined the impact of 120-dGA hypothalamo-pituitary disconnection (HPD), which prevents corticotrope maturation, on responsiveness of pituitary cells isolated from 140-dGA fetuses. Cells were stimulated with AVP, and the formation of IP3 and secretion of ACTH were assessed. Significantly less IP3 was formed, and ACTH secreted in cells from HPD compared with control fetuses (IP3 and ACTH levels were 50% and 35% lower, respectively). Results from the HPD study demonstrate that the ontogenic changes in IP3 after AVP require an intact hypothalamic-pituitary-adrenal axis. These findings suggest that heightened second messenger generation may be a key reason for increased ACTH secretory responsiveness to AVP in the late gestation sheep fetus.

Altered platelet serotonin 5-HT2A receptor density but not second messenger inositol trisphosphate levels in drug-free schizophrenic patients

2003 ◽  
Vol 118 (2) ◽  
pp. 165-174 ◽  
Author(s):  
Belén Arranz ◽  
Pilar Rosel ◽  
Salvador Sarró ◽  
Nicolás Ramirez ◽  
Rosa Dueñas ◽  
...  
Keyword(s):  
Inositol Trisphosphate ◽  
Second Messenger ◽  
Receptor Density ◽  
Platelet Serotonin ◽  
Schizophrenic Patients ◽  
Drug Free

scholarly journals Thrombin-induced inositol trisphosphate production by rabbit platelets is inhibited by ethanol

1988 ◽  
Vol 251 (1) ◽  
pp. 279-284 ◽  
Author(s):  
M L Rand ◽  
J D Vickers ◽  
R L Kinlough-Rathbone ◽  
M A Packham ◽  
J F Mustard
Keyword(s):  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Inositol Trisphosphate ◽  
Thromboxane A2 ◽  
Second Messenger ◽  
Inhibitory Effect ◽  
Thromboxane B2 ◽  
Rabbit Platelets ◽  
Platelet Functions ◽  
Stimulation Of

Ethanol has an inhibitory effect on some platelet functions, but the mechanisms by which it exerts this effect are not known. Using suspensions of washed platelets, we observed that ethanol (1-9 mg/ml) did not affect the aggregation of rabbit platelets stimulated with ADP (0.5-10 microM). When platelets were prelabelled with 5-hydroxy[14C]tryptamine, aggregation and secretion of granule contents in response to thrombin (0.01-0.10 unit/ml) were not inhibited by ethanol, but these responses to thrombin at lower concentrations (less than 0.01 unit/ml) were inhibited by ethanol (2-4 mg/ml). Platelets were prelabelled with [3H]inositol so that increases in inositol phosphates upon stimulation could be assessed by measuring the amount of label in these compounds. ADP-induced increases in IP (inositol phosphate) and IP2 (inositol bisphosphate) were not affected by ethanol. IP3 (inositol trisphosphate) was not changed by ADP or ethanol. Although ethanol did not affect the increases in IP, IP2 and IP3 caused by stimulation of platelets with thrombin at concentrations greater than 0.01 unit/ml, ethanol did inhibit the increases observed at 2 and 3 min in these inositol phosphates caused by lower concentrations of thrombin (less than 0.01 unit/ml). Since ADP did not cause formation of IP3 in rabbit platelets, and since no thromboxane B2 was detected in platelets stimulated with the lower concentrations of thrombin, it is unlikely that the inhibitory effect of ethanol in IP3 formation was due to effects on further stimulation of platelets by released ADP or by thromboxane A2. Ethanol may inhibit platelet responses to thrombin by inhibiting the production of the second messenger, IP3.

scholarly journals Calcium modulates the generation of inositol 1,3,4-trisphosphate in human platelets by the activation of inositol 1,4,5-trisphosphate 3-kinase

1988 ◽  
Vol 253 (3) ◽  
pp. 789-794 ◽  
Author(s):  
J L Daniel ◽  
C A Dangelmaier ◽  
J B Smith
Keyword(s):  
Phospholipase C ◽  
Inositol Trisphosphate ◽  
Second Messenger ◽  
Dienoic Acid ◽  
Human Platelets ◽  
Inositol 1,4,5 Trisphosphate

We observed that more total inositol trisphosphate (InsP3) was formed when human platelets were stimulated with agonists (15-hydroxy-9,11-azo-prosta-5,13-dienoic acid or thrombin) in the presence of extracellular Ca2+ than in its absence. Analysis of the InsP3 by h.p.l.c. indicated that the increased InsP3 formed in the presence of extracellular Ca2+ was primarily the 1,3,4-trisphosphate [Ins(1,3,4)P3]. In addition, more inositol 1,3,4,5-tetrakisphosphate (InsP4) was formed in the presence of extracellular Ca2+. Experiments conducted with electrically permeabilized platelets demonstrated that conversion of [3H]Ins(1,4,5)P3 to [3H]InsP4 in platelets was Ca2+-dependent, with half-maximal conversion observed at approx. 2.5 microM-Ca2+. By contrast, dephosphorylation of [3H]InsP4 to [3H]Ins(1,3,4)P3 was not activated by Ca2+. A partially purified preparation of Ins(1,4,5)P3 3-kinase from human platelets was found to be insensitive to Ca2+, but addition of calmodulin restored Ca2+-sensitivity to the kinase, increasing its activity about 5-fold. These results show that in human platelets the metabolism of Ins(1,4,5)P3 is regulated by Ca2+-calmodulin, and suggest that the metabolites of Ins(1,4,5)P3 may also have important second-messenger functions in platelets, and are consistent with the hypothesis that the activation of phospholipase C is not dependent on extracellular Ca2+.

Second messenger systems as sites of drug action

1992 ◽  
Vol 99 (1-2) ◽  
pp. 1-17
Author(s):  
W. C. Bowman
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
Ion Channel ◽  
G Protein ◽  
Inositol Trisphosphate ◽  
Second Messenger ◽  
Drug Action ◽  
Surface Receptors ◽  
Second Messenger Systems ◽  
Near Future

Synopsis:Transmembrane signalling from cell surface receptors occurs by two broad mechanisms: (i) the rapid (ms) direct opening of an ion channel, where the ion channel is a component of the receptor complex (e.g. the nicotinic acetylcholine receptor); and (ii) the more slow (s) modulation of a membrane enzyme or more distant ion channel. Most of the examples of this second mechanism involve a GTP-binding protein or so–called G-protein, and the production of a second messenger. The production of nitric oxide is a special case in that it is eventually produced as a result of the activity of the second messenger ïnositol trisphosphate. The nitric oxide then diffuses into a second cell to give rise to the production of an additional ‘second’ messenger, cyclic GMP.All of the surface receptors themselves exist as a number of subtypes. Additionally, most of the components of the second messenger systems – G-proteins, adenylyl cyclase, guanylyl cyclase, phosphoinositidase, C, inositol trisphosphate receptors, protein kinase A, protein kinase G, protein kinase C, cyclic nucleotide phosphodiesterases, and the enzymes involved in phosphatidylinositol resynthesis – occur in a number of isoforms. Furthermore, all the enzymes are controlled in their activity by a number of co-factors and other modulators. This diversity provides the potential for selective drug action, a potential which is already being exploited and which will be increasingly so in the near future.

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