Role of intracellular pH as a signal in the stimulation of pancreatic islets

1988 ◽  
Vol 16 (5) ◽  
pp. 807-808
Author(s):  
LEONARD BEST ◽  
ELIZABETH A. BONE ◽  
JUDITH E. MEATS ◽  
STEPHEN TOMLINSON
Keyword(s):  
Pancreatic Islets ◽  
Intracellular Ph ◽  
Stimulation Of

scholarly journals Cytoplasmic [Ca2+] and intracellular pH in lymphocytes. Role of membrane potential and volume-activated Na+/H+ exchange.

1987 ◽  
Vol 89 (2) ◽  
pp. 185-213 ◽  
Author(s):  
S Grinstein ◽  
S Cohen
Keyword(s):  
Protein Kinase C ◽  
Membrane Potential ◽  
Protein Kinase ◽  
Intracellular Ph ◽  
Enzyme Treatment ◽  
Membrane Hyperpolarization ◽  
Kinase C ◽  
Free Media ◽  
Stimulation Of

The effect of elevating cytoplasmic Ca2+ [( Ca2+]i) on the intracellular pH (pHi) of thymic lymphocytes was investigated. In Na+-containing media, treatment of the cells with ionomycin, a divalent cation ionophore, induced a moderate cytoplasmic alkalinization. In the presence of amiloride or in Na+-free media, an acidification was observed. This acidification is at least partly due to H+ (equivalent) uptake in response to membrane hyperpolarization since: it was enhanced by pretreatment with conductive protonophores, it could be mimicked by valinomycin, and it was decreased by depolarization with K+ or gramicidin. In addition, activation of metabolic H+ production also contributes to the acidification. The alkalinization is due to Na+/H+ exchange inasmuch as it is Na+ dependent, amiloride sensitive, and accompanied by H+ efflux and net Na+ gain. A shift in the pHi dependence underlies the activation of the antiport. The effect of [Ca2+]i on Na+/H+ exchange was not associated with redistribution of protein kinase C and was also observed in cells previously depleted of this enzyme. Treatment with ionomycin induced significant cell shrinking. Prevention of shrinking largely eliminated the activation of the antiport. Moreover, a comparable shrinking produced by hypertonic media also activated the antiport. It is concluded that stimulation of Na+/H+ exchange by elevation of [Ca2+]i is due, at least in part, to cell shrinking and does not require stimulation of protein kinase C.

Stimulation of H+ secretion by CO2 in turtle bladder: role of intracellular pH, exocytosis, and calcium

1990 ◽  
Vol 258 (1) ◽  
pp. R222-R231
Author(s):  
J. A. Arruda ◽  
G. Dytko ◽  
Z. Talor
Keyword(s):  
Intracellular Calcium ◽  
Intracellular Ph ◽  
Fluorescent Dye ◽  
Isolated Cells ◽  
Cell Calcium ◽  
Turtle Bladder ◽  
Early Increase ◽  
Stimulation Of ◽  
Related Increase

We studied the interaction of intracellular pH, exocytosis, and cell calcium on the stimulation of H+ secretion by CO2 in turtle bladder. Intracellular pH was continuously monitored by the fluorescent dye 6-carboxyfluorescein and exocytosis was monitored by the release of mucosal fluorescein dextran. The initial stimulation of H+ secretion by 1 or 5% CO2 added to the serosal solution was accompanied by a similar and temporally related increase in exocytosis. Furthermore, a decrease in intracellular pH seems necessary for the early increase in H+ secretion and exocytosis. Because calcium plays an important role in exocytosis, we measured intracellular calcium in isolated cells with the fluorescent dye quin2. An increase in intracellular calcium (from 50 to 100 nM) was observed in isolated turtle bladder epithelial cells gassed with 5% CO2. To further evaluate the role of intracellular calcium on H+ secretion and exocytosis we utilized agents that alter cell calcium such as trifluoperazine and lanthanum. In the presence of CO2 these agents blocked partially the increase in H+ secretion and exocytosis but did not affect the decrease in intracellular H+. In conclusion, exocytosis, intracellular pH, and intracellular calcium play a key role in mediating CO2-stimulated H+ secretion in the turtle bladder.

Potassium-Induced Stimulation of Glutamate Uptake in Mouse Cerebral Astrocytes: The Role of Intracellular pH

2002 ◽  
Vol 66 (1) ◽  
pp. 169-176 ◽  
Author(s):  
Michael G. Judd ◽  
Tavarekere N. Nagaraja ◽  
Neville Brookes
Keyword(s):  
Intracellular Ph ◽  
Glutamate Uptake ◽  
Stimulation Of

Cytosolic calcium, oxygen consumption and the intracellular pH of stimulated neutrophils

1988 ◽  
Vol 8 (1) ◽  
pp. 65-76 ◽  
Author(s):  
Patricia E. Nasmith ◽  
Sergio Grinstein
Keyword(s):  
Oxygen Consumption ◽  
Intracellular Ph ◽  
Cytosolic Calcium ◽  
Cytoplasmic Ph ◽  
Acid Generation ◽  
Cytoplasmic Acidification ◽  
Free Media ◽  
Stimulation Of

The cytoplasmic pH undergoes a biphasic change when neutrophils are activated. The role of Ca2+ in initiating these changes was investigated. No correlation was found between the increased cytosolic [Ca2+] and the stimulation of the Na+/H+ antiport. Similarly, the cytoplasmic acidification elicited by activation in Na+-free media was found to be unrelated to [Ca2+]. Reversal of Na+/H+ exchange was also ruled out as the source of the acidification. Data using a variety of soluble activators indicate that metabolic acid generation is largely responsible for the observed drop in cytoplasmic pH.

Effects of CO2-induced acidification on the fatigue resistance of single mouse muscle fibers at 28°C

1998 ◽  
Vol 85 (2) ◽  
pp. 478-483 ◽  
Author(s):  
Joseph D. Bruton ◽  
Jan Lännergren ◽  
Håkan Westerblad
Keyword(s):  
Skeletal Muscle ◽  
Intracellular Ph ◽  
Muscle Fibers ◽  
Initial Value ◽  
Mouse Muscle ◽  
Tetanic Force ◽  
Muscle Ph ◽  
Initial Peak ◽  
Stimulation Of

The role of reduced muscle pH in the development of skeletal muscle fatigue is unclear. This study investigated the effects of lowering skeletal muscle intracellular pH by exposure to 30% CO2 on the number of isometric tetani needed to induce significant fatigue. Isolated single mouse muscle fibers were stimulated repetitively at intervals of 4–2.5 s by using 80-Hz, 400-ms tetani at 28°C in Tyrode solution bubbled with either 5 or 30% CO2. Stimulation continued until tetanic force had fallen to 40% of the initial value. Exposure to 30% CO2 caused a significant fall in intracellular pH of ∼0.3 pH unit but did not cause any significant changes in initial peak tetanic force. During the course of repetitive stimulation, intracellular pH fell by ∼0.3 pH unit in both normal and acidified fibers. The number of tetani needed to reduce force to 40% of the initial value was not significantly different in 5 and 30% CO2Tyrode. The sole effect of acidosis was to reduce the rate of relaxation of force, especially in fatigued fibers. It is concluded that, at 28°C, acidosis per se does not accelerate the development of fatigue during repeated tetanic stimulation of isolated mouse skeletal muscle fibers.

scholarly journals The role of protein kinase C in the desensitization of rat pancreatic islets to cholinergic stimulation

1998 ◽  
Vol 159 (2) ◽  
pp. 287-295 ◽  
Author(s):  
EJ Verspohl ◽  
A Wienecke
Keyword(s):  
Protein Kinase C ◽  
Insulin Secretion ◽  
Protein Kinase ◽  
Pancreatic Islets ◽  
Repetitive Stimulation ◽  
Cholinergic Stimulation ◽  
Kinase C ◽  
Pkc Inhibitors ◽  
Stimulation Of

It is well known that protein kinase C (PKC) plays an important role in mediating insulin secretion in response to cholinergic stimulation. In various cells PKC also mediates a desensitization process. The role of PKC for homologous desensitization of the insulin response to repetitive stimulation with the muscarinic agonist carbachol (CCh) was investigated in perifusion experiments using isolated rat pancreatic islets. Repetitive (six times) stimulation with CCh (100 microM) reduced insulin secretion over time (up to 50% during the second challenge). This was not a toxic effect since the desensitizing effect was mostly washed out after 45 min. When PKC was downregulated by long term preincubation (20 h) with 200 nM phorbol 12-myristate 13-acetate (TPA), the initial stimulation of insulin release by CCh was reduced by 50%, and a desensitization by further CCh stimulation was no longer obvious. In contrast, when other compounds with different mechanisms of actions for inactivating PKC were used, i.e. PKC inhibitors such as staurosporin (100 nM), Ro 31-8220 (5 microM) or PKC peptide(19-31), the insulin secretion in response to CCh was reduced but the desensitization was not abolished. When PKC was downregulated or inhibited by the above methods, the PKC activator phorbol 12-myristate 13-acetate (TPA; 200 nM) was no longer able to evoke an increase in insulin secretion during static incubation, i.e. these control experiments indicate a real PKC inhibition. When heparin (50 microg/ml), an inhibitor of G-protein coupled receptor kinase (GRK), was used, the desensitization of the cholinergic stimulation of insulin release remained unchanged. The data indicate that PKC plays a role in CCh-mediated insulin secretion and also show a desensitization of this effect after repetitive stimulation with CCh. The data further indicate that specific PKC isoenzymes that are inhibited by staurosporin or Ro 31-8220 do not take part in the desensitization process, while isoenzymes that are downregulated by TPA are involved. It may be speculated that a hitherto unknown PKC isoenzyme that is downregulated by TPA but not by the other used PKC inhibitors is involved in the desensitization process, or that a nonspecific effect of TPA is involved. Members of the GRK family are not involved in the desensitization process of CCh.

Stimulation of Ca(2+)-dependent exocytosis of the sperm acrosome by cAMP acting downstream of phospholipase A2

Reproduction ◽  
2000 ◽  
pp. 57-68 ◽  
Author(s):  
J Garde ◽  
ER Roldan
Keyword(s):  
Arachidonic Acid ◽  
Phospholipase A2 ◽  
Phospholipase C ◽  
Phosphodiesterase Inhibitors ◽  
Dibutyryl Camp ◽  
Camp Phosphodiesterase ◽  
Ram Sperm ◽  
Camp Formation ◽  
Stimulation Of

Spermatozoa undergo exocytosis in response to agonists that induce Ca2+ influx and, in turn, activation of phosphoinositidase C, phospholipase C, phospholipase A2, and cAMP formation. Since the role of cAMP downstream of Ca2+ influx is unknown, this study investigated whether cAMP modulates phospholipase C or phospholipase A2 using a ram sperm model stimulated with A23187 and Ca2+. Exposure to dibutyryl-cAMP, phosphodiesterase inhibitors or forskolin resulted in enhancement of exocytosis. However, the effect was not due to stimulation of phospholipase C or phospholipase A2: in spermatozoa prelabelled with [3H]palmitic acid or [14C]arachidonic acid, these reagents did not enhance [3H]diacylglycerol formation or [14C]arachidonic acid release. Spermatozoa were treated with the phospholipase A2 inhibitor aristolochic acid, and dibutyryl-cAMP to test whether cAMP acts downstream of phospholipase A2. Under these conditions, exocytosis did not occur in response to A23187 and Ca2+. However, inclusion of dibutyryl-cAMP and the phospholipase A2 metabolite lysophosphatidylcholine did result in exocytosis (at an extent similar to that seen when cells were treated with A23187/Ca2+ and without the inhibitor). Inclusion of lysophosphatidylcholine alone, without dibutyryl-cAMP, enhanced exocytosis to a lesser extent, demonstrating that cAMP requires a phospholipase A2 metabolite to stimulate the final stages of exocytosis. These results indicate that cAMP may act downstream of phospholipase A2, exerting a regulatory role in the exocytosis triggered by physiological agonists.

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