Isoproterenol potentiates α-adrenergic and muscarinic receptor-mediated Ca2+ response in rat parotid cells

1999 ◽  
Vol 276 (6) ◽  
pp. C1282-C1287 ◽  
Author(s):  
Akihiko Tanimura ◽  
Akihiro Nezu ◽  
Yosuke Tojyo ◽  
Yoshito Matsumoto
Keyword(s):  
Protein Kinase ◽  
Phospholipase C ◽  
Muscarinic Receptor ◽  
Maximal Response ◽  
Response Curves ◽  
Dependent Protein Kinase ◽  
Camp Pathway ◽  
Parotid Cells ◽  
Dependent Protein ◽  
Rat Parotid

The effects of the cAMP pathway on the Ca2+ response elicited by phospholipase C-coupled receptor stimulations were studied in rat parotid cells. Although 1 μM isoproterenol (Iso) itself had no effect on the cytosolic Ca2+ concentration, the pretreatment with Iso potentiated Ca2+ responses evoked by phenylephrine. The potentiating effect of Iso was attributed to a shifting of the concentration-response curves of phenylephrine to the left and an increase in the maximal response. Half-maximal potentiation occurred at 3 nM Iso. Iso also potentiated the Ca2+ response elicited by carbachol. The potentiating effect of Iso was mimicked by forskolin (10 μM) and dibutyryl adenosine 3′,5′-cyclic monophosphate (2 mM) and was blocked by 10 μM H-89. Iso potentiated the phenylephrine-induced Ca2+response in the absence of extracellular Ca2+, but Iso did not increase the inositol trisphosphate (IP3) production induced by phenylephrine. These results suggest that the potentiation of the Ca2+ response can be attributed to a sensitization of IP3 receptors by cAMP-dependent protein kinase.

Mechanical strain-enhanced fetal lung cell proliferation is mediated by phospholipase C and D and protein kinase C

1995 ◽  
Vol 268 (5) ◽  
pp. L729-L738 ◽  
Author(s):  
M. Liu ◽  
J. Xu ◽  
J. Liu ◽  
M. E. Kraw ◽  
A. K. Tanswell ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Phospholipase C ◽  
Second Messengers ◽  
Mechanical Strain ◽  
Rat Lung ◽  
Dependent Protein Kinase ◽  
Fetal Rat ◽  
Fetal Rat Lung ◽  
Dependent Protein ◽  
Pkc Activation

The signaling pathways by which intermittent strain (60 cycles/min, 15 min/h) regulates proliferation of mixed fetal rat lung cell in vitro have been investigated. Adenosine 3',5'-cyclic monophosphate (cAMP) content and cAMP-dependent protein kinase (PKA) activity were not affected by strain. The stimulatory effect of strain on DNA synthesis was also not influenced by the cyclic nucleotide-dependent protein kinase inhibitors H-8 or HA-1004, the adenylate cyclase inhibitor SQ-22536, or a PKA inhibitor and cAMP antagonist, adenosine 3',5'-cyclic monophosphothioate (Rp-cAMPS). In contrast, intracellular concentrations of two second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), were dramatically increased after a short period of strain. This increase in second messengers was accompanied by an increased tyrosine phosphorylation of phospholipase C-gamma 1. Phospholipase D activity was also increased by strain. Mechanical strain elicited a shift in the subcellular distribution of PKC activity from cytosol to membranes shortly after the onset of strain. The specific activity of PKC in the membranes increased 6- to 10-fold within 5-15 min and remained increased throughout a 48-h period of intermittent strain. Strain-induced PKC activation and DNA synthesis were blocked by the PKC inhibitors H-7, staurosporine, and calphostin C, as well as by the phospholipase C inhibitor U-73,122. We conclude that mechanical strain of mixed fetal rat lung cells activates phospholipid turnover via phospholipases, followed by PKC activation, which then triggers the downstream events that lead to cell proliferation.

scholarly journals Characteristics of selective activation of cyclic AMP-dependent protein kinase isoenzymes by calcitonin and prostaglandin E2 in human breast cancer cells

1984 ◽  
Vol 224 (2) ◽  
pp. 361-370 ◽  
Author(s):  
S A Livesey ◽  
G Collier ◽  
J D Zajac ◽  
B E Kemp ◽  
T J Martin
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Prostaglandin E2 ◽  
Maximal Response ◽  
Human Breast ◽  
Selective Activation ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Mcf 7

The characteristics of the cyclic AMP-dependent protein kinase isoenzyme response to calcitonin stimulation have been studied in two human breast cancer cell lines, T47D and MCF 7. Both cell lines possess calcitonin receptors, a calcitonin-responsive adenylate cyclase and the two isoenzymes of the cyclic AMP-dependent protein kinase, types I and II. The adenylate cyclase also responds to prostaglandin E2. Acute activation of the cyclic AMP-dependent protein kinase isoenzymes was determined by using a modification of a multiple small anion exchange column method [Livesey, Kemp, Re, Partridge & Martin (1982) J. Biol. Chem. 257, 14983-14987]. Control experiments showed that post-extraction activation did not influence the data. Calcitonin caused a rapid, selective activation of isoenzyme II in the T 47D cells with half-maximal response at 10(-10)M, and persisting for at least 24h. In MCF 7 cells calcitonin also caused a highly selective activation of isoenzyme II with half-maximal response at 5 × 10(-11) M, but the response was transient with a return to basal isoenzyme activity by 4-6 h. At this time further addition of calcitonin did not restimulate the cyclic AMP-dependent kinase activity. In neither cell line did calcitonin treatment result in activation of isoenzyme I. Prostaglandin E2, on the other hand, the only significant alternative agonist of adenylate cyclase in T 47D cells, activated isoenzymes I and II to an equal extent in these cells, illustrating that two hormones activating adenylate cyclase in the one cell type might exert different effects by their selective actions upon protein kinase isoenzymes.

An Essential Function of a Phosphoinositide-Specific Phospholipase C Is Relieved by Inhibition of a Cyclin-Dependent Protein Kinase in the Yeast Saccharomyces cerevisiae

Genetics ◽  
1998 ◽  
Vol 148 (1) ◽  
pp. 33-47 ◽  
Author(s):  
Jeffrey S Flick ◽  
Jeremy Thorner
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Kinase ◽  
Phospholipase C ◽  
Growth Defect ◽  
Temperature Sensitive ◽  
Complete Medium ◽  
Restrictive Temperature ◽  
Dependent Protein Kinase ◽  
Yeast Saccharomyces Cerevisiae ◽  
Dependent Protein

Abstract The PLC1 gene product of Saccharomyces cerevisiae is a homolog of the δ isoform of mammalian phosphoinositide-specific phospholipase C (PI-PLC). We found that two genes (SPL1 and SPL2), when overexpressed, can bypass the temperature-sensitive growth defect of a plc1Δ cell. SPL1 is identical to the PHO81 gene, which encodes an inhibitor of a cyclin (Pho80p)-dependent protein kinase (Pho85p) complex (Cdk). In addition to overproduction of Pho81p, two other conditions that inactivate this Cdk, a cyclin (pho80Δ) mutation and growth on low-phosphate medium, also permitted growth of plc1Δ cells at the restrictive temperature. Suppression of the temperature sensitivity of plc1Δ cells by pho80Δ does not depend upon the Pho4p transcriptional regulator, the only known substrate of the Pho80p/Pho85p Cdk. The second suppressor, SPL2, encodes a small (17-kD) protein that bears similarity to the ankyrin repeat regions present in Pho81p and in other known Cdk inhibitors. Both pho81Δ and spl2Δ show a synthetic phenotype in combination with plc1Δ. Unlike single mutants, plc1Δ pho81Δ and plc1Δ spl2Δ double mutants were unable to grow on synthetic complete medium, but were able to grow on rich medium.

A neurochemical mechanism for hypoxia-induced anapyrexia

2002 ◽  
Vol 283 (6) ◽  
pp. R1412-R1422 ◽  
Author(s):  
Alexandre A. Steiner ◽  
Maria J. A. Rocha ◽  
Luiz G. S. Branco
Keyword(s):  
Protein Kinase ◽  
Body Temperature ◽  
Preoptic Region ◽  
Dependent Protein Kinase ◽  
Hypoxia Exposure ◽  
Cgmp Dependent Protein Kinase ◽  
Camp Pathway ◽  
Male Wistar Rats ◽  
Dependent Protein ◽  
Camp And Cgmp

Hypoxia evokes a regulated decrease in body temperature, a response that has been termed anapyrexia, but the mechanisms involved are poorly understood. Therefore, the present study was undertaken to test the hypothesis that hypoxia-induced anapyrexia results from the activation of cAMP- and cGMP-dependent pathways in the preoptic region (PO). Adult male Wistar rats weighing 230–260 g were used. Body temperature was monitored by biotelemetry, and the levels of cAMP and cGMP were determined in the anteroventral third ventricular region (AV3V), where the PO is located. Using immunohistochemistry, we observed that the PO contains a high density of cAMP- and cGMP-containing cells. Interestingly, hypoxia exposure raised the levels of cAMP and cGMP in the AV3V. Intra-PO microinjection of Rp-cAMPS, an inhibitor of cAMP-dependent protein kinase, attenuated hypoxia-induced anapyrexia. Similarly, intra-PO microinjection of the mixed β-adrenoceptor/serotonin (5-HT1A) receptor antagonist propranolol also impaired the drop in body temperature in response to hypoxia. The reduction in body temperature evoked by intra-PO serotonin, but not epinephrine, was blocked by Rp-cAMPS, indicating the involvement of a preoptic serotonin-cAMP pathway in the development of anapyrexia. Moreover, microinjection of N G-monomethyl-l-arginine, an inhibitor of nitric oxide (NO) synthesis, or Rp-cGMPS, an inhibitor of cGMP-dependent protein kinase, into the PO also attenuated hypoxia-induced anapyrexia. In conclusion, the present study supports that hypoxia-induced anapyrexia results from the activation of the serotonin-cAMP and NO-cGMP pathways in the PO.

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