scholarly journals Acute stimulation of glucagon secretion by linoleic acid results from GPR40 activation and [Ca2+]i increase in pancreatic islet α-cells

2011 ◽  
Vol 210 (2) ◽  
pp. 173-179 ◽  
Author(s):  
Li Wang ◽  
Yufeng Zhao ◽  
Baosong Gui ◽  
Rongguo Fu ◽  
Feng Ma ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Linoleic Acid ◽  
Signaling Pathways ◽  
Phospholipase C ◽  
Glucagon Secretion ◽  
Free Calcium ◽  
Downstream Signaling ◽  
Intracellular Ca ◽  
Stimulation Of

The role of free fatty acids (FFAs) in glucagon secretion has not been well established, and the involvement of FFA receptor GPR40 and its downstream signaling pathways in regulating glucagon secretion are rarely demonstrated. In this study, it was found that linoleic acid (LA) acutely stimulated glucagon secretion from primary cultured rat pancreatic islets. LA at 20 and 40 μmol/l dose-dependently increased glucagon secretion both at 3 mmol/l glucose and at 15 mmol/l glucose, although 15 mmol/l glucose reduced basal glucagon levels. LA induced an increase in cytoplasmic free calcium concentrations ([Ca2+]i) in identified rat α-cells, which is reflected by increased Fluo-3 intensity under confocal microscopy recording. The increase in [Ca2+]i was partly inhibited by removal of extracellular Ca2+ and eliminated overall by further exhaustion of intracellular Ca2+ stores using thapsigargin treatment, suggesting that both Ca2+ release and Ca2+ influx contributed to the LA-stimulated increase in [Ca2+]i in α-cells. Double immunocytochemical stainings showed that GPR40 was expressed in glucagon-positive α-cells. LA-stimulated increase in [Ca2+]i was blocked by inhibition of GPR40 expression in α-cells after GPR40-specific antisense treatment. The inhibition of phospholipase C activity by U73122 also blocked the increase in [Ca2+]i by LA. It is concluded that LA activates GPR40 and phospholipase C (and downstream signaling pathways) to increase Ca2+ release and associated Ca2+ influx through Ca2+ channels, resulting in increase in [Ca2+]i and glucagon secretion.

scholarly journals Role of calcium and calmodulin in ciliary stimulation induced by acetylcholine

2001 ◽  
Vol 280 (1) ◽  
pp. C100-C109 ◽  
Author(s):  
Orna Zagoory ◽  
Alex Braiman ◽  
Larisa Gheber ◽  
Zvi Priel
Keyword(s):  
Phospholipase C ◽  
Muscarinic Receptors ◽  
Elevated Level ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Combined Effect ◽  
Molecular Events ◽  
Intracellular Ca ◽  
Stimulation Of

The goal of this work was to elucidate the molecular events underlying stimulation of ciliary beat frequency (CBF) induced by acetylcholine (ACh) in frog esophagus epithelium. ACh induces a profound increase in CBF and in intracellular Ca2+ concentration ([Ca2+]i) through M1 and M3 muscarinic receptors. The [Ca2+]i slowly decays to the basal level, while CBF stabilizes at an elevated level. These results suggest that ACh triggers Ca2+-correlated and -uncorrelated modes of ciliary stimulation. ACh response is abolished by the phospholipase C (PLC) inhibitor U-73122 and by depletion of intracellular Ca2+ stores but is unaffected by reduction of extracellular Ca2+ concentration and by blockers of Ca2+influx. Therefore, ACh activates PLC and mobilizes Ca2+solely from intracellular stores. The calmodulin inhibitors W-7 and calmidazolium attenuate the ACh-induced increase in [Ca2+]i but completely abolish the elevation in CBF. Therefore, elevation of [Ca2+]i is necessary for CBF enhancement but does not lead directly to it. The combined effect of Ca2+ elevation and of additional factors, presumably mobilized by Ca2+-calmodulin, results in a robust CBF enhancement.

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.

scholarly journals Adrenaline Stimulation of Phospholipid Metabolism in Adipocyte Ghosts

1987 ◽  
Vol 40 (4) ◽  
pp. 405
Author(s):  
David Mann ◽  
Audrey M Bersten
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Linoleic Acid ◽  
Adenylate Cyclase ◽  
Phospholipid Metabolism ◽  
Dependent Manner ◽  
Long Chain Fatty Acids ◽  
Membrane Phospholipids ◽  
Dose Dependent ◽  
Stimulation Of

The incorporation of long-chain fatty acids into phospholipids has been detected in adipocyte ghosts that were incubated with [1_14 C] stearic, [1_14 C] linoleic or [l_14C] arachidonic acid. Adrenaline and adenosine activated this incorporation within 15 s of exposure of the ghosts to the hormones and the response was dose dependent. Maximum incorporation of labelled linoleic acid occurred at 10-5 M adrenaline and 10-7 M adenosine. The a-agonist phenylephrine and the ~-agonist isoproterenol were also shown to stimulate the incorporation of fatty acid in a dose dependent manner. Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol were each labelled preferentially with linoleic or arachidonic acid. p-Bromophenacylbromide, quinacrine and centrophenoxine inhibited the adrenaline-stimulated incorporation of fatty acids into ghost membrane phospholipids, and p-bromophenacylbromide also reduced the activation of adenylate cyclase by adrenaline. NaF, an activator of adenylate cyclase, like adrenaline, stimulated the incorporation of linoleic acid into ghost membrane phospholipids.

scholarly journals LDL activates signaling pathways leading to an increase in cytosolic free calcium and stimulation of CD11b expression in monocytes

2003 ◽  
Vol 44 (7) ◽  
pp. 1332-1340 ◽  
Author(s):  
Ki Hoon Han ◽  
Yiming Chen ◽  
Mi Kyung Chang ◽  
Yoon Chan Han ◽  
Jae-Hyung Park ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Free Calcium ◽  
Cytosolic Free Calcium ◽  
Cd11b Expression ◽  
Stimulation Of

scholarly journals The Role of Arachidonic and Linoleic Acid Derivatives in Pathological Pregnancies and the Human Reproduction Process

2020 ◽  
Vol 21 (24) ◽  
pp. 9628
Author(s):  
Małgorzata Szczuko ◽  
Justyna Kikut ◽  
Natalia Komorniak ◽  
Jacek Bilicki ◽  
Zbigniew Celewicz ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Fatty Acids ◽  
Linoleic Acid ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Overweight And Obesity ◽  
Male Reproduction ◽  
Human Reproduction ◽  
In Pregnancy

The aim of the available literature review was to focus on the role of the proinflammatory mediators of AA and LA derivatives in pathological conditions related to reproduction and pregnancy. Arachidonic (AA) and linoleic acid (LA) derivatives play important roles in human fertility and the course of pathological pregnancies. Recent studies have demonstrated that uncontrolled inflammation has a significant impact on reproduction, spermatogenesis, endometriosis, polycystic ovary syndrome (PCOS) genesis, implantation, pregnancy and labor. In addition, cyclooxygenase-mediated prostaglandins and AA metabolite levels are higher in women’s ovarian tissue when suffering from PCOS. It has been demonstrated that abnormal cyclooxygenase-2 (COX-2) levels are associated with ovulation failure, infertility, and implantation disorders and the increase in 9-HODE/13-HODE was a feature recognized in PCOS patients. Maintaining inflammation without neutrophil participation allows pregnant women to tolerate the fetus, while excessive inflammatory activation may lead to miscarriages and other pathological complications in pregnancies. Additionally AA and LA derivatives play an important role in pregnancy pathologies, e.g., gestational diabetes mellitus, preeclampsia (PE), and fetal growth, among others. The pathogenesis of PE and other pathological states in pregnancy involving eicosanoids have not been fully identified. A significant expression of 15-LOX-1,2 was found in women with PE, leading to an increase in the synthesis of AA and LA derivatives, such as hydroxyeicozatetraenoic acids (HETE) and hydroxyoctadecadiene acids (HODE). Synthesis of the metabolites 5-, 8-, 12-, and 15-HETE increased in the placenta, while 20-HETE increased only in umbilical cord blood in women with preeclampsia compared to normal pregnancies. In obese women with gestational diabetes mellitus (GDM) an increase in epoxygenase products in the cytochrome P450 (CYP) and the level of 20-HETE associated with the occurrence of insulin resistance (IR) were found. In addition, 12- and 20-HETE levels were associated with arterial vasoconstriction and epoxyeicosatrienoic acids (EETs) with arterial vasodilatation and uterine relaxation. Furthermore, higher levels of 5- and 15-HETE were associated with premature labor. By analyzing the influence of free fatty acids (FFA) and their derivatives on male reproduction, it was found that an increase in the AA in semen reduces its amount and the ratio of omega-6 to omega-3 fatty acids showed higher values in infertile men compared to the fertile control group. There are several studies on the role of HETE/HODE in relation to male fertility. 15-Hydroperoxyeicosatetraenoic acid may affect the integrity of the membrane and sperm function. Moreover, the incubation of sperm with physiologically low levels of prostaglandins (PGE2/PGF2α) improves the functionality of human sperm. Undoubtedly, these problems are still insufficiently understood and require further research. However, HETE and HODE could serve as predictive and diagnostic biomarkers for pregnancy pathologies (especially in women with risk factors for overweight and obesity). Such knowledge may be helpful in finding new treatment strategies for infertility and the course of high-risk pregnancies.

Involvement of phospholipase C in endothelin 1–induced stimulation of Ca++ channels and basilar artery contraction in rabbits

2006 ◽  
Vol 105 (2) ◽  
pp. 288-293 ◽  
Author(s):  
Yoshifumi Kawanabe ◽  
Tomoh Masaki ◽  
Nobuo Hashimoto
Keyword(s):  
Phospholipase C ◽  
Essential Role ◽  
Ca Channels ◽  
Endothelin 1 ◽  
Nonselective Cation Channels ◽  
Basilar Arteries ◽  
Independent Cascade ◽  
Dependent Pathway ◽  
Stimulation Of

Object Endothelin 1 (ET-1) is a major cause of cerebral vasospasm after subarachnoid hemorrhage (SAH), and extracellular Ca++ influx plays an essential role in ET-1–induced vasospasm. The authors recently demonstrated that ET-1 activates two types of Ca++-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and a store-operated Ca++ channel (SOCC) in vascular smooth-muscle cells located in the basilar arteries (BAs) of rabbits. In the present study, they investigate the effects of phospholipase C (PLC) on ET-1–induced activation of these Ca++ channels and BA contraction by using the PLC inhibitor U73122. Methods To determine which Ca++ channels are activated via a PLC-dependent pathway, these investigators monitored the intracellular free Ca++ concentration ([Ca++]i). The role of PLC in ET-1–induced vascular contraction was examined by performing a tension study of rabbit BA rings. The U73122 inhibited the ET-1–induced transient increase in [Ca++]i, which resulted from mobilization of Ca++; from the intracellular store. Phospholipase C also inhibited ET-1–induced extracellular Ca++ influx through the SOCC and NSCC-2, but not through the NSCC-1. The U73122 inhibited the ET-1–induced contraction of the rabbit BA rings, which depended on extracellular Ca++ influx through the SOCC and NSCC-2. Conclusions These results indicate the following. 1) The SOCC and NSCC-2 are stimulated by ET-1 via a PLC-dependent cascade whereas NSCC-1 is stimulated via a PLC-independent cascade. 2) The PLC is involved in the ET-1–induced contraction of rabbit BA rings, which depends on extracellular Ca++ influx through the SOCC and NSCC-2.

scholarly journals Anaphylactic shock depends on endothelial Gq/G11

2009 ◽  
Vol 206 (2) ◽  
pp. 411-420 ◽  
Author(s):  
Hanna Korhonen ◽  
Beate Fisslthaler ◽  
Alexandra Moers ◽  
Angela Wirth ◽  
Daniel Habermehl ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Anaphylactic Shock ◽  
Platelet Activating Factor ◽  
Severe Allergic Reaction ◽  
Downstream Signaling ◽  
Systemic Anaphylaxis ◽  
Multiple Organs ◽  
Nitric Oxide Formation ◽  
G Protein Coupled

Anaphylactic shock is a severe allergic reaction involving multiple organs including the bronchial and cardiovascular system. Most anaphylactic mediators, like platelet-activating factor (PAF), histamine, and others, act through G protein–coupled receptors, which are linked to the heterotrimeric G proteins Gq/G11, G12/G13, and Gi. The role of downstream signaling pathways activated by anaphylactic mediators in defined organs during anaphylactic reactions is largely unknown. Using genetic mouse models that allow for the conditional abrogation of Gq/G11- and G12/G13-mediated signaling pathways by inducible Cre/loxP-mediated mutagenesis in endothelial cells (ECs), we show that Gq/G11-mediated signaling in ECs is required for the opening of the endothelial barrier and the stimulation of nitric oxide formation by various inflammatory mediators as well as by local anaphylaxis. The systemic effects of anaphylactic mediators like histamine and PAF, but not of bacterial lipopolysaccharide (LPS), are blunted in mice with endothelial Gαq/Gα11 deficiency. Mice with endothelium-specific Gαq/Gα11 deficiency, but not with Gα12/Gα13 deficiency, are protected against the fatal consequences of passive and active systemic anaphylaxis. This identifies endothelial Gq/G11-mediated signaling as a critical mediator of fatal systemic anaphylaxis and, hence, as a potential new target to prevent or treat anaphylactic reactions.

Sign in / Sign up

Export Citation Format

Share Document