scholarly journals Synergistic control of Ca2+ mobilization in permeabilized mouse L1210 lymphoma cells by inositol 2,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate

1990 ◽  
Vol 271 (2) ◽  
pp. 549-553 ◽  
Author(s):  
P J Cullen ◽  
R F Irvine ◽  
A P Dawson

L1210 lymphoma cells were permeabilized with digitonin, and the ability of Ins(2,4,5)P3 and Ins(1,3,4,5)P4 to mobilize intracellular Ca2+ was studied. At high doses of Ins(2,4,5)P3 Ca2+ was rapidly released from intracellular stores, and prior or subsequent addition of Ins(1,3,4,5)P4 had no discernible effect. However, the Ca2(+)-mobilizing action of low (threshold or just above) concentrations of Ins(2,4,5)P3 was markedly enhanced by Ins(1,3,4,5)P4, which alone caused no mobilization of Ca2+; this phenomenon was shown not to be due to protection of Ins(2,4,5)P3 by the Ins(1,3,4,5)P4 against hydrolysis. The ability of the pre-addition of Ins(1,3,4,5)P4 to enhance subsequent Ins(2,4,5)P3-induced Ca2+ mobilization was always seen whether or not the free Ca2+ concentration was low (pCa = 7) or high (pCa = 6). However, at low Ca2+, Ins(1,3,4,5)P4 could cause a further mobilization if added after the Ins(2,4,5)P3, whereas at higher Ca2+ values Ins(1,3,4,5)P4 was only able to affect Ca2+ if added before Ins(2,4,5)P3. These effects of Ins(1,3,4,5)P4 were not, at the same concentration, mimicked by a random mixture of InsP4 isomers obtained by partial acid hydrolysis of phytic acid, by Ins(1,3,4)P3 or by Ins(1,3,4,5,6)P5, and they were shown not to be due to enzymic generation of Ins(1,4,5)P3 from Ins(1,3,4,5)P4 by (a) the absence of any detectable production of Ins(1,4,5)P3 if radiolabelled Ins(1,3,4,5)P4 was used, or (b) the observation that Ins(1,3,4,5,6)P5 could mimic Ins(1,3,4,5)P4 provided that higher doses were used; this inositol phosphate, when added radiolabelled, yielded only trace quantities of D/L-Ins(1,4,5,6)P4, which itself does not mobilize Ca2+. We interpret these results overall to mean that in these cells there is a small proportion of the Ins(2,4,5)P3-mobilizable Ca2+ pools which can only be mobilized in the presence of Ins(1,3,4,5)P4 [or at the least, Ins(1,3,4,5)P4 can help Ins(2,4,5)P3 to gain access to them]. The significance of this conclusion is discussed in the light of current concepts of the second messenger function of Ins(1,3,4,5)P4.

1979 ◽  
Vol 47 (1) ◽  
pp. 26-31 ◽  
Author(s):  
M. King ◽  
N. Viires

The effect of methacholine chloride (M) on tracheal mucus was investigated in three conscious tracheostomized dogs. Aerosols of M in concentrations of 2--32 mg/ml were delivered intratracheally for 1 min. Mucus was sampled with a cytology brush at 2 min postchallenge and at irregular intervals thereafter. The mechanical properties of each sample were determined in the magnetic microrheometer, and correlated with mucociliary transportability as assayed by the frog palate technique. With high doses of M, there was an increase in volume of secretion collected per unit time. The elastic modulus (G′) at 2 min postchallenge went up (to 1.5 x 2.3 x control for 16 and 32 mg/ml, respectively) then fell below control before returning to base line after 30 or 45 min. With low doses of M (2--8 mg/ml) the secretion rate was also above control, but only a decrease in G′ (to 0.54 x control) was observed. The decrease in G′ at low doses did not significantly alter the frog palate transport rate; however, the increase at higher doses did impede mucociliary transport.


1985 ◽  
Vol 248 (5) ◽  
pp. G532-G538
Author(s):  
M. V. Singer ◽  
W. Niebel ◽  
K. H. Uhde ◽  
D. Hoffmeister ◽  
H. Goebell

In dogs with gastric and pancreatic fistulas, we studied the effect of intravenous atropine in doses ranging from 0.9 to 58 nmol X kg-1 X h-1 on the pancreatic secretory response to secretin before and after truncal vagotomy. Truncal vagotomy did not alter the incremental bicarbonate response to secretin. Before and after truncal vagotomy, 7 nmol X kg-1 X h-1 and all higher doses of atropine sulfate significantly decreased the bicarbonate response to low doses (5.2 and 10.3 pmol X kg-1 X h-1) of secretin but had no significant effect on responses to high doses (20.5 and 41 pmol X kg-1 X h-1). The inhibitory potency of the effective doses of atropine did not differ significantly. Secretin did not stimulate pancreatic protein output above basal. Truncal vagotomy reduced protein output basally and during secretin by about 50%. Before and after truncal vagotomy, 7 nmol X kg-1 X h-1 and all higher doses of atropine significantly decreased protein output basally and during secretin. Secretin and truncal vagotomy did not alter basal heart rate. Only the three highest doses (14, 29, and 58 nmol X kg-1 X h-1) of atropine significantly increased heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)


1957 ◽  
Vol 79 (10) ◽  
pp. 2559-2565 ◽  
Author(s):  
N. J. Hipp ◽  
M. L. Groves ◽  
T. L. McMeekin

1974 ◽  
Vol 139 (3) ◽  
pp. 535-545 ◽  
Author(s):  
G. B. Fincher ◽  
W. H. Sawyer ◽  
B. A. Stone

1. An arabinogalactan-peptide from wheat endosperm was studied by using physicochemical techniques and some aspects of its chemical structure were determined. 2. The arabinogalactan-peptide is a non-associating, polydisperse macromolecule ([unk]=22000) which exhibits only minor non-ideal effects in aqueous solution. 3. Examination of the products of partial acid hydrolysis of the polysaccharide component showed that arabinose is present in the α-l-arabinofuranosyl configuration, and i.r.-absorption spectroscopy and optical-rotation studies suggest that the d-galactopyranose residues are linked by glycosidic linkages in the β-anomeric configuration. 4. The arabinogalactan is linked to a peptide which represents 8% (w/w) of the arabinogalactan-peptide and which may be present as a molecular core. Partial degradation of the polymer by successive treatment with oxalic acid and NaOH showed that the linkage between polysaccharide and peptide involves galactose and hydroxyproline residues and is glycosidic in nature. A tentative model is proposed for the structure of the wheat endosperm arabinogalactan-peptide. 5. The subcellular location and function of the arabinogalactan-peptide is discussed in relation to previous work with related molecules.


1997 ◽  
Vol 273 (1) ◽  
pp. R407-R413 ◽  
Author(s):  
A. A. Romanovsky ◽  
C. T. Simons ◽  
M. Szekely ◽  
V. A. Kulchitsky

Experimentally, systemic inflammation induced by a bolus intravenous injection of lipopolysaccharide (LPS) may be accompanied by three different thermoregulatory responses: monophasic fever (the typical response to low doses of LPS), biphasic fever (medium doses), and hypothermia (high doses). In our recent study [Romanovsky, A. A., V. A. Kulchitsky, C. T. Simons, N. Sugimoto, and M. Szekely. Am. J. Physiol. (Regulatory Integrative Comp. Physiol.). In press], monophasic fever did not occur in subdiaphragmatically vagotomized rats. In the present work, we asked whether vagotomy affects the two other types of thermoregulatory response. Adult Wistar rats were vagotomized (or sham operated) and had an intravenous catheter implanted. On day 28 postvagotomy, the thermal responses to the intravenous injection of Escherichia coli LPS (0, 1, 10, 100, or 1,000 micrograms/kg) were tested in either a neutral (30 degrees C) or slightly cool (25 degrees C) environment. Three major results were obtained. 1) In the sham-operated rats, the 1 microgram/kg dose of LPS caused at 30 degrees C a monophasic fever with a maximal colonic temperature (Tc) rise of approximately 0.6 degree C; this response was abated (no Tc changes) in the vagotomized rats. 2) At 30 degrees C, all responses to higher doses of LPS (10-1,000 micrograms/kg) were represented by biphasic fevers (the higher the dose, the less pronounced the first and the more pronounced the second phase was); none of these biphasic fevers was altered in the vagotomized animals. 3) In response to the 1,000 micrograms/kg dose at 25 degrees C, hypothermia occurred: Tc changed by -0.5 +/- 0.1 degree C (nadir); this hypothermia was exaggerated (-1.1 +/- 0.1 degrees C) in the vagotomized rats. It is concluded that vagal afferentation may be important in the mediation of the response to minor amounts of circulating LPS, whereas the response to larger amounts is brought about mostly (if not exclusively) by nonvagal mechanisms. This difference may be explained by the dose-dependent mechanisms of the processing of exogenous pyrogens. Vagotomized animals also appear to be more sensitive to the hypothermizing action of LPS in a cool environment; the mechanisms of this phenomenon remain speculative.


1965 ◽  
Vol 208 (6) ◽  
pp. 1093-1099 ◽  
Author(s):  
John K. Healy ◽  
Carlos Barcena ◽  
J. M. Brian O'Connell ◽  
George E. Schreiner

The renal and pressor actions of angiotensin in relation to dose were studied in unanesthetized dogs. Low doses caused depression of urine flow, electrolyte excretion, glomerular filtration rate (GFR), and Cpah. With higher doses, the initial depression of urine flow, GFR, and Cpah was greater, but subsequently these functions rose toward control values. In fact, diuresis occurred, accompanied by natriuresis, chloruresis, and kaliuresis. The natriuresis occurred at a time when GFR was significantly depressed. In longer experiments at high doses it was found that the natriuresis declined after 50 min despite continued angiotensin infusion; however, potassium excretion gradually increased throughout. These results help clarify the confusing literature regarding the effects of angiotensin on renal function in dogs and also support the hypothesis that angiotensin can block tubular sodium reabsorption. The pressor response was found to be proportional to the logarithm of the dose of angiotensin. It was also inversely related to the control blood pressure of the dog.


1986 ◽  
Vol 6 (7) ◽  
pp. 613-619 ◽  
Author(s):  
Michael P. Schrey ◽  
Alison M. Read ◽  
Philip J. Steer

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.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Vijayapandi Pandy ◽  
Megala Narasingam ◽  
Thubasni Kunasegaran ◽  
Dharmani Devi Murugan ◽  
Zahurin Mohamed

This study examined the effect of methanolic extract ofMorinda citrifoliaLinn. (MMC) and its bioactive principles, scopoletin and rutin, on dopamine- and noradrenaline-evoked contractility in isolated rat vas deferens preparations. MMC (1–40 mg/mL), scopoletin (1–200 μg/mL), and rutin hydrate (0.6–312.6 μg/mL) dose-dependently inhibited the contractility evoked by submaximal concentrations of both dopamine and noradrenaline, respectively. Haloperidol and prazosin, reference dopamine D2, andα1-adrenoceptors antagonists significantly reversed the dopamine- and noradrenaline-induced contractions, respectively, in a dose-dependent manner. Interestingly, MMCper seat higher doses (60–100 mg/mL) showed dose-dependent contractile response in rat vas deferens which was partially inhibited by high doses of haloperidol but not by prazosin. These results demonstrated the biphasic effects of MMC on dopaminergic system; that is, antidopaminergic effect at lower concentrations (<40 mg/mL) and dopaminergic agonistic effect at higher concentrations (>60 mg/mL). However, similar contractile response at high doses of scopoletin (0.5–5 mg/mL) and rutin hydrate (0.5–5 mg/mL)per sewas not observed. Therefore, it can be concluded that the bioactive principles of MMC, scopoletin, and rutin might be responsible for the antidopaminergic and antiadrenergic activities of MMC.


The molecular events involved in the cellular actions of insulin remain unexplained. Some of the acute actions of the hormone may be due to the intracellular generation of a chemical substance which modulates certain enzyme activities. Such an enzymemodulating substance has been identified as an inositol phosphate-glycan, produced by the insulin-sensitive hydrolysis of a glycosyl-phosphatidylinositol (glycosyl-Ptdlns) precursor. This precursor glycolipid is structurally similar to the glycosylphosphoinositide membrane protein anchor. The exposure of fat, liver or muscle cells to insulin results in the hydrolysis of glycosyl-Ptdlns, giving rise to the inositol phosphate glycan and diacylglycerol. This hydrolysis reaction is catalysed by a glycosyl-PtdIns-specific phospholipase C. This enzyme has been characterized and purified from a plasma membrane fraction of liver. This reaction also results in the acute release of certain glycosyl-Ptdlns-anchored proteins from the cell surface. Elucidation of the functional role of glycosyl-phosphoinositides in the generation of second messengers or the release of proteins may provide further insights into the pleiotropic nature of insulin action.


1986 ◽  
Vol 110 (3) ◽  
pp. 389-393 ◽  
Author(s):  
P. L. Canonico ◽  
W. D. Jarvis ◽  
A. M. Judd ◽  
R. M. MacLeod

ABSTRACT The hydrolysis of membrane phosphatidylinositol to yield [3H]labelled inositol phosphates by anterior pituitary cells was stimulated significantly by angiotensin II, TRH and neurotensin over a broad range of concentrations. These secretagogues also stimulated release of prolactin. Although the coincident incubation of dopamine with these agents resulted in a marked diminution of prolactin release, no concomitant reduction in inositol phosphate production was observed. In addition, bromocriptine, a potent agonist of dopamine, also proved ineffective in blunting stimulated phosphatidylinositol catabolism. Although it slightly inhibited basal rates of inositol tris-, bis- and monophosphate production, these results show that the secretagogue-mediated enhancement of phosphatidylinositol catabolism may be correlated with an increased release of prolactin and that the inhibition of hormone release produced by dopamine is not achieved by reducing basal or secretagogue-mediated inositol phosphate production. J. Endocr. (1986) 110, 389–393


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