scholarly journals Arachidonic acid is functioning as a second messenger in activating the Ca2+ entry process on H1-histaminoceptor stimulation in DDT1 MF-2 cells

1995 ◽  
Vol 305 (3) ◽  
pp. 859-864 ◽  
Author(s):  
L van der Zee ◽  
A Nelemans ◽  
A den Hertog
Keyword(s):  
Arachidonic Acid ◽  
Extracellular Space ◽  
Channel Blocker ◽  
Vas Deferens ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Second Messenger ◽  
Slow Decline ◽  
K Current ◽  
Ca2 Channels

This study was carried out to identify the cellular component activating the histamine-stimulated Ca2+ entry in vas-deferens-derived DDT1 MF-2 cells. H1-histaminoceptor stimulation resulted in a rise in intracellular Ca2+ concentration, caused by Ca2+ release from inositol phosphate-sensitive Ca2+ stores and Ca2+ entry from the extracellular space, accompanied by a transient Ca(2+)-activated outward K+ current. The histamine-evoked K+ current was still observed after preventing inositol phosphate-induced Ca2+ mobilization by intracellularly applied heparin. This current was activated by Ca2+ entry from the extracellular space, because it was abolished in the presence of the Ca(2+)-channel blocker La3+ or under Ca(2+)-free conditions. H1-histaminoceptor-activated Ca2+ entry was also observed in the presence of intracellularly applied Ins(1,4,5)P3 and Ins(1,3,4,5)P4, depleting their respective Ca2+ stores and pre-activating the inositol phosphate-regulated Ca2+ entry. Thus the ability of histamine to activate Ca2+ entry independently of Ca2+ mobilization and the formation of inositol phosphates suggests that another component is involved to initiate the Ca(2+)-entry process. It was observed that H1-histaminoceptor stimulation resulted in a pronounced release of arachidonic acid (AA) in DDT1 MF-2 cells. Exogenously applied AA induced a concentration-dependent increase in internal Ca2+ due to activation of Ca2+ entry from the extracellular space. Slow inactivation of the AA-sensitive Ca2+ channels is suggested by the slow decline in Ca2+ entry. In accord, the histamine-induced Ca2+ entry was not observed with AA-pre-activated Ca2+ channels. Inhibition of the lipoxygenase and cyclo-oxygenase pathway did not affect the AA-induced Ca2+ and the concomitant K+ current were decreased in the presence of AA and caused by Ca2+ mobilization from internal stores. Blocking this internal Ca2+ release by heparin, in the presence of AA, resulted in abolition of the histamine-induced Ca(2+)-regulated K+ current. These observations show that AA, released on H1-histaminoceptor stimulation in DDT1 MF-2 cells, is functioning as a second messenger to activate plasma-membrane Ca2+ channels promoting Ca2+ entry from the extracellular space.

Oxytocin and vasopressin stimulate inositol phosphate production in human gestational myometrium and decidua cells

1986 ◽  
Vol 6 (7) ◽  
pp. 613-619 ◽  
Author(s):  
Michael P. Schrey ◽  
Alison M. Read ◽  
Philip J. Steer
Keyword(s):  
Arachidonic Acid ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Diacylglycerol Lipase ◽  
Inositol 1 ◽  
Inositol Phosphate Production ◽  
Acid Accumulation ◽  
Free Arachidonic Acid ◽  
Hydrolysis Of ◽  
Related Increase

The involvement of phosphoinositide hydrolysis in the action of oxytocin and vasopressin on the uterus was investigated in gestational myometrium and decidua cells by measuring the production of inositol phosphates. Both peptides stimulated a dose related increase in all three inositol phosphates in myometrium. This may be related to the control of sarcoplasmic Ca++ levels in the myometrium. Oxytocin and vasopressin also stimulated inositol 1-phosphate (IP) production in decidua cells. The hydrolysis of phosphatidylinositol by decidua homogenates exhibited a precursor-product relationship for diacylglycerol and arachidonic acid accumulation. Hence both peptides may mobilise free arachidonic acid, for prostaglandin biosynthesis, from decidua cell phosphoinositides by the sequential action of phospholipase C and diacylglycerol lipase.

scholarly journals Functional Triads Consisting of Ryanodine Receptors, Ca2+ Channels, and Ca2+-Activated K+ Channels in Bullfrog Sympathetic Neurons

2000 ◽  
Vol 116 (5) ◽  
pp. 697-720 ◽  
Author(s):  
Tenpei Akita ◽  
Kenji Kuba
Keyword(s):  
High Speed ◽  
Channel Blocker ◽  
Ganglion Cells ◽  
Sympathetic Neurons ◽  
Ryanodine Receptors ◽  
Bk Channels ◽  
K Channel ◽  
Sk Channels ◽  
K Current ◽  
Ca2 Channels

Fluorescent ryanodine revealed the distribution of ryanodine receptors in the submembrane cytoplasm (less than a few micrometers) of cultured bullfrog sympathetic ganglion cells. Rises in cytosolic Ca2+ ([Ca2+]i) elicited by single or repetitive action potentials (APs) propagated at a high speed (150 μm/s) in constant amplitude and rate of rise in the cytoplasm bearing ryanodine receptors, and then in the slower, waning manner in the deeper region. Ryanodine (10 μM), a ryanodine receptor blocker (and/or a half opener), or thapsigargin (1–2 μM), a Ca2+-pump blocker, or ω-conotoxin GVIA (ω-CgTx, 1 μM), a N-type Ca2+ channel blocker, blocked the fast propagation, but did not affect the slower spread. Ca2+ entry thus triggered the regenerative activation of Ca2+-induced Ca2+ release (CICR) in the submembrane region, followed by buffered Ca2+ diffusion in the deeper cytoplasm. Computer simulation assuming Ca2+ release in the submembrane region reproduced the Ca2+ dynamics. Ryanodine or thapsigargin decreased the rate of spike repolarization of an AP to 80%, but not in the presence of iberiotoxin (IbTx, 100 nM), a BK-type Ca2+-activated K+ channel blocker, or ω-CgTx, both of which decreased the rate to 50%. The spike repolarization rate and the amplitude of a single AP-induced rise in [Ca2+]i gradually decreased to a plateau during repetition of APs at 50 Hz, but reduced less in the presence of ryanodine or thapsigargin. The amplitude of each of the [Ca2+]i rise correlated well with the reduction in the IbTx-sensitive component of spike repolarization. The apamin-sensitive SK-type Ca2+-activated K+ current, underlying the afterhyperpolarization of APs, increased during repetitive APs, decayed faster than the accompanying rise in [Ca2+]i, and was suppressed by CICR blockers. Thus, ryanodine receptors form a functional triad with N-type Ca2+ channels and BK channels, and a loose coupling with SK channels in bullfrog sympathetic neurons, plastically modulating AP.

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.

Stimulation of prolactin release by dopamine withdrawal: role of calcium influx

1994 ◽  
Vol 267 (5) ◽  
pp. E789-E794 ◽  
Author(s):  
K. A. Gregerson ◽  
R. Chuknyiska ◽  
N. Golesorkhi
Keyword(s):  
Channel Blocker ◽  
Inositol Phosphates ◽  
Calcium Influx ◽  
Pituitary Cells ◽  
Induced Changes ◽  
Camp Levels ◽  
Ca2 Channels ◽  
Stimulation Of ◽  
Spiking Activity

Withdrawal of dopamine (DA), a neurotransmitter that inhibits prolactin (PRL) release from the anterior pituitary, stimulates PRL release with transient (30- to 45-min) secretory rates that exceed those observed before application of DA ("PRL rebound"). Using patch-clamp methods on identified rat lactotropes, we have demonstrated that a period of increased Ca(2+)-spiking activity follows recovery from the DA-induced hyperpolarization. The present experiments used dissociated pituitary cells to identify the relative roles of adenosine 3',5'-cyclic monophosphate (cAMP), inositol phosphates, and the enhanced influx of Ca2+ in the rebound secretion of PRL. Rebound secretion of PRL after DA withdrawal was completely blocked by the Ca2+ channel blocker verapamil (20 microM), which also inhibited spontaneous Ca(2+)-spiking activity. DA-induced changes in cAMP levels could be completely dissociated from the PRL rebound. Production of inositol phosphates rose after DA withdrawal but was secondary to the influx of Ca2+. These data demonstrate that influx of extracellular Ca2+ through verapamil-sensitive channels is a critical step in inducing PRL release after DA withdrawal. This finding supports our theory that DA-induced hyperpolarization recruits previously inactivated Ca2+ channels and upon DA washout the enhanced influx of Ca2+ through these voltage-regulated channels supports the rebound release of PRL.

Evidence for direct non-genomic effects of triiodothyronine on bone rudiments in rats: Stimulation of the inositol phosphate second messenger system

1991 ◽  
Vol 125 (6) ◽  
pp. 603-608 ◽  
Author(s):  
Peter Lakatos ◽  
Paula H. Stern
Keyword(s):  
Plasma Membrane ◽  
Thyroid Hormones ◽  
Time Course ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Second Messenger ◽  
Cytosolic Calcium ◽  
Membrane Receptors ◽  
Free Calcium ◽  
Stimulation Of

Abstract. Thyroid hormones increase cytosolic free calcium by binding to plasma membrane receptors in several tissues. This calcium increase appears to initiate extranuclear effects in these tissues. Increases in cytosolic calcium are often a consequence of stimulation of inositol phosphate second messenger pathway. Several calcemic hormones act via this signal transduction route. Therefore we investigated the effects of the metabolically active T3 and the inactive analogues 3,5-diiodotyrosine and rT3 on the inositol phosphate pathway in fetal rat limb bone cultures prelabeled with [3H]myoinositol. Labelled inositol and inositol phosphates were separated by HPLC. There was a significant increase in the radioactivity in inositol bis- and trisphosphates after 1 min of exposure to 10−7 mol/l T3. Stimulation was also observed at 10−6 mol/l T3, but not at 10−5 mol/l. Time course studies demonstrated a rapid effect of T3 on inositol phosphates within 30 seconds that lasted through 5 min. After 20 min incubation with T3, no increase was observed in inositol mono- and bisphosphates, and a decrease was seen in inositol trisphosphate. Pretreatment with indomethacin prevented these effects of T3. 3,5-diiodothyrosine and rT3 did not affect inositol phosphate metabolism. These results suggest the existence of plasma membrane-associated receptors for T3 in bone, in addition to the nuclear receptors demonstrated previously. The role of these receptors in the effects of thyroid hormones on bone remains to be established.

Second messenger specificity of the inositol trisphosphate receptor: reappraisal based on novel inositol phosphates

1994 ◽  
Vol 266 (2) ◽  
pp. C429-C436 ◽  
Author(s):  
S. DeLisle ◽  
T. Radenberg ◽  
M. R. Wintermantel ◽  
C. Tietz ◽  
J. B. Parys ◽  
...  
Keyword(s):  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Second Messenger ◽  
The Novel ◽  
High Potency ◽  
Inositol Trisphosphate Receptor ◽  
Highly Active ◽  
Intracellular Receptor ◽  
Trisphosphate Receptor ◽  
Very High

To further understand how the second messenger D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] interacts with its intracellular receptor, we injected 47 highly purified inositol phosphate (InsP) positional isomers in Xenopus oocytes and compared their potency in releasing intracellular Ca2+. The potency of the Ca(2+)-releasing InsPs spanned four orders of magnitude. Seven compounds, including the novel inositol 1,2,4,5-tetrakisphosphate [D/L-Ins (1,2,4,5)P4] and D/L-Ins(1,4,6)P3, had a very high potency. All of these highly active InsPs shared the following structure: two D-trans-equatorial phosphates (eq-P) and one equatorial hydroxyl (eq-OH) attached to ring carbons D-4, D-5, and D-6 (or to the structurally equivalent D-1, D-6, and D-5 carbons). This permissive structure was not sufficient for Ca2+ release, because it was also found in two inactive compounds, Ins(1,6)P2 and Ins(1,3,6)P3. To be active, InsPs also required the structural equivalent of a D-3 eq-OH and/or a D-1 eq-P. Together, our data reveal how the structure of the InsP molecule affects its ability to release Ca2+.

scholarly journals Prolactin induces an inward current through voltage-independent Ca2+ channels in Chinese hamster ovary cells stably expressing prolactin receptor

1998 ◽  
Vol 21 (1) ◽  
pp. 85-95 ◽  
Author(s):  
D Ratovondrahona ◽  
M Fahmi ◽  
B Fournier ◽  
MF Odessa ◽  
R Skryma ◽  
...  
Keyword(s):  
Chinese Hamster Ovary ◽  
Inositol Phosphates ◽  
Calcium Influx ◽  
Inositol Phosphate ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Target Cells ◽  
Patch Clamp Technique ◽  
Open Probability ◽  
Ca2 Channels

There is still only limited understanding of the early steps of prolactin (PRL) signal transduction in target cells. Recent studies have identified some of the essential first steps: these include the rapid association of the PRL receptor with JAK tyrosine kinases and tyrosine phosphorylation of a number of proteins, including members of the signal transducer and activator of transcription (Stats) family. On the other hand, binding of PRL to its receptor is rapidly followed by calcium influx. However, PRL-induced ionic events and the related ionic channels involved have not been clearly established. This work was undertaken to characterise the channels responsible for calcium influx and to obtain an insight into their activation processes. Using the patch-clamp technique in the cell-attached configuration, single Ca2+ channel currents were recorded following PRL application (10 nM) in Chinese hamster ovary (CHO) cells stably expressing PRL receptor (CHO-E32). Statistical analysis showed that the recorded currents were voltage-independent, with a slope conductance of 16 pS. Although these channels were present in excised patches, the fact that PRL was unable to activate them suggested that a soluble cytoplasmic component may be required. Application of the purified inositol phosphate, Ins(1,3,4,5)P4 (2 microM), to the inside of the excised patch membrane activated the voltage-independent 16 pS Ca2+ channel. The open probability (Popen) was enhanced. The inositol phosphates Ins(1,2,3,4,5)P5 and Ins(1,4,5)P3 did not affect channel activity while InsP6 (20 microM) had some effect, although less marked than that of Ins(1,3,4,5)P4. Using the anion-exchange HPLC technique, we then studied the effects of PRL (10 nM) on the turnover of inositol phosphates (InsPs) in CHO-E32. Our studies showed that PRL induces rapid increases in the production of Ins(1,3,4,5)P4 (207% at 30 s), InsP5 (171% at 30 s), and InsP6 (241% at 30 s). Conversely, Ins(1,4,5)P3 showed a transient decrease at 5 s, accompanied by a concomitant increase in Ins(1,3,4,5)P4, suggesting that the former could be transiently phosphorylated to produce the latter. Comparison of the production kinetics of Ins(1,4,5)P3, Ins(1,3,4,5)P4, InsP5, and InsP6 indicated the possibility of additional metabolic routes which have yet to be determined. This study suggests that PRL promotes Ca2+ entry through voltage-independent Ca2+ channels that may be activated by Ins(1,3,4,5)P4 and InsP6.

scholarly journals Endothelial inositol phosphate generation and prostacyclin production in response to G-protein activation by AlF4−

1989 ◽  
Vol 264 (3) ◽  
pp. 703-711 ◽  
Author(s):  
M K Magnússon ◽  
H Halldórsson ◽  
M Kjeld ◽  
G Thorgeirsson
Keyword(s):  
Arachidonic Acid ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
G Protein ◽  
Pertussis Toxin ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Ionophore A23187 ◽  
Kinase C

In order to elucidate the role of guanine-nucleotide-binding proteins (G-proteins) in endothelial prostacyclin (PGI2) production, human umbilical vein endothelial cells, prelabelled with either [3H]inositol or [3H]arachidonic acid, were stimulated with the non-specific G-protein activator aluminium fluoride (AlF4-). AlF4- caused a dose- and time-dependent generation of inositol phosphates, release of arachidonic acid and production of PGI2. The curves for the three events were similar. When the cells were stimulated in low extracellular calcium (60 nM), they released [3H]arachidonic acid and produced PGI2, but depleting the intracellular Ca2+ stores by pretreatment with the Ca2+ ionophore A23187 totally inhibited both events, although the cells still responded when extracellular Ca2+ was added. The Ca2+ ionophore did not inhibit the generation of inositol phosphates in cells maintained at low extracellular Ca2+. Pertussis toxin pretreatment (14 h) altered neither inositol phosphate nor PGI2 production in response to AlF4-. To investigate the functional role of the diacylglycerol/protein kinase C arm of the phosphoinositide system, the cells were pretreated with the protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA) or the protein kinase C inhibitor 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H7). TPA inhibited the AlF4(-)-induced inositol phosphate generation but stimulated both the release of arachidonic acid and the production of PGI2. H7 had opposite effects both on inositol phosphate generation and on PGI2 production. These results suggest that AlF4(-)-induced PGI2 production is mediated by a pertussis-toxin-insensitive G-protein which activates the phosphoinositide second messenger system. This production of PGI2 can be modulated by protein kinase C activation, both at the level of inositol phosphate generation and at the level of arachidonic acid release.

Glucocorticoids act rapidly in vitro to attenuate second messenger responses to ACTH secretagogues in rats

1989 ◽  
Vol 122 (2) ◽  
pp. 545-551 ◽  
Author(s):  
S. A. Nicholson ◽  
B. Gillham
Keyword(s):  
Dose Response ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Hormone Secretion ◽  
Second Messenger ◽  
Response Curves ◽  
Delayed Effects ◽  
Pituitary Glands ◽  
The Time Domain

ABSTRACT Fragments of rat anterior pituitary glands incubated in vitro and challenged with either of two ACTH secretagogues were used to investigate the extent to which the acute, biphasic, feedback-like inhibitory effects on hormone secretion exerted by the synthetic glucocorticoid dexamethasone were related to alterations in second messenger responses. Addition of dexamethasone was shown to cause both an immediate inhibition (fast inhibition) of the release of ACTH-like immunoreactivity induced by arginine vasopressin (AVP) or corticotrophin-releasing factor (CRF-41), and also an inhibition that occurred after removal of the steroid and was maximal 90 min after its introduction (early delayed inhibition). The accumulation of adenosine 3′,5′-monophosphate (cAMP) in the tissue was enhanced in a dose-related manner by CRF-41, as was that of phosphate esters of inositol (inositol phosphates) by AVP. The dose–response curve for the effect of CRF-41 on cAMP production was markedly shifted to the right by dexamethasone acting in the time-domain of fast inhibition (i.e. the response was attenuated, but not abolished). Application of the steroid during the same time-period reduced significantly the inositol phosphate response induced by the higher concentration of AVP tested (3000 mmol/l), but had no effect on the action of a lower concentration (30 mmol/l). In contrast, the cAMP and inositol phosphate dose–response curves to CRF-41 and AVP respectively were unaffected by the glucocorticoid when it was applied at the time which generated early delayed inhibition of ACTH release. It is concluded that part of the fast inhibitory action of dexamethasone on ACTH secretion in vitro (but not its delayed effects) involves a rapid alteration of second messenger responses to secretagogues, but the precise mechanism underlying this process remains to be established. Journal of Endocrinology (1989) 122, 545–551

scholarly journals Evidence that muscarinic cholinergic receptors selectively interact with either the cyclic AMP or the inositol phosphate second-messenger response systems

1987 ◽  
Vol 247 (3) ◽  
pp. 793-796 ◽  
Author(s):  
J R Hepler ◽  
A R Hughes ◽  
T K Harden
Keyword(s):  
Cyclic Amp ◽  
Pertussis Toxin ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Second Messenger ◽  
Cholinergic Receptor ◽  
Receptor Activation ◽  
Phosphoinositide Hydrolysis ◽  
Response Systems ◽  
Muscarinic Cholinergic

The relative capacities of muscarinic cholinergic receptor (MR) and bradykinin (BK)-receptor activation to increase phosphoinositide hydrolysis and to increase cytosolic Ca2+ were compared in NG108-15 neuroblastoma x glioma and 1321N1 human astrocytoma cells. In 1321N1 cells, the muscarinic cholinergic agonist carbachol and BK each stimulated a concentration-dependent accumulation of inositol phosphates (K0.5 approximately 10 microM and approximately 10 nM respectively) and a rapid increase in cytosolic Ca2+ as determined by quin2 fluorescence. In NG108-15 cells, BK alone stimulated a pertussis-toxin-insensitive accumulation of inositol phosphates (K0.5 approximately 10 nM) under conditions in which pertussis toxin completely inhibited MR-mediated inhibition of adenylate cyclase. BK also stimulated a rapid increase in cytosolic Ca2+ in NG108-15 cells. In contrast, no MR-mediated increase in phosphoinositide hydrolysis or change in cytosolic Ca2+ concentration was observed in NG108-15 cells. These results support the idea that MR selectively interact with either the cyclic AMP or the inositol phosphate second-messenger systems.

Sign in / Sign up

Export Citation Format

Share Document