Adenosine A1 receptor-mediated inhibition of myocardial norepinephrine release involves neither phospholipase C nor protein kinase C but does involve adenylyl cyclase

2006 ◽  
Vol 84 (5) ◽  
pp. 573-577 ◽  
Author(s):  
Frank Schütte ◽  
Christof Burgdorf ◽  
Gert Richardt ◽  
Thomas Kurz
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Adenylyl Cyclase ◽  
Phospholipase C ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Direct Stimulation ◽  
Kinase C ◽  
Gf 109203X ◽  
Stimulation Of

Stimulation of adenosine A1 receptors in the heart exerts cardioprotective effects by inhibiting norepinephrine (NE) release from sympathetic nerve endings. The intraneuronal signal transduction triggered by presynaptic adenosine A1 receptors is still not completely understood. The objective of the present study was to determine whether phospholipase C (PLC), protein kinase C (PKC), and adenylyl cyclase (AC) are involved in the adenosine A1 receptor-mediated inhibition of endogenous (stimulation-induced) NE release in isolated Langendorff-perfused rat hearts as an approach to elucidate their role in the cardiovascular system. Activation of adenosine A1-receptors with 2-chloro-N6-cyclopentyladenosine (CCPA) decreased cardiac NE release by ~40%. Inhibition of PLC with 1-[6-[[(17b)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U 73122) as well as inhibition of PKC with 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl)maleimide (GF 109203X) slightly but significantly decreased NE release; however, the suppressive effect of CCPA on NE release was not modulated by U 73122 or GF 109203X. Blockade of AC with 9-(tetrahydro-2′-furyl)adenine (SQ 22536) reversed the inhibitory effect of CCPA on sympathetic neurotransmitter release irrespective of whether PKC was pharmacologically activated by phorbol 12-myristate 13-acetate or was not activated, indicating a PKC-independent but AC-dependent mechanism. Direct stimulation of AC with forskolin increased NE release by ∼20%; an effect that was antagonized by either CCPA or SQ 22536. These data suggest that the adenosine A1 receptor-mediated inhibition of NE release does not involve PLC or PKC but does involve AC.

Regulation of oxytocin secretion by the ovine corpus luteum: effect of activators of protein kinase C

1990 ◽  
Vol 124 (2) ◽  
pp. 225-232 ◽  
Author(s):  
J. J. Hirst ◽  
G. E. Rice ◽  
G. Jenkin ◽  
G. D. Thorburn
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Corpus Luteum ◽  
Phospholipase C ◽  
Tissue Slices ◽  
Kinase C ◽  
Luteal Tissue ◽  
Dose Dependent ◽  
Stimulation Of

ABSTRACT The effect of protein kinase C activation and dibutyryl cyclic AMP on oxytocin secretion by ovine luteal tissue slices was investigated. Several putative regulators of luteal oxytocin secretion were also examined. Oxytocin was secreted by luteal tissue slices at a basal rate of 234·4 ± 32·8 pmol/g per h (n = 24) during 60-min incubations.Activators of protein kinase C: phorbol 12,13-dibutyrate (n = 8), phorbol 12-myristate,13-acetate (n = 4) and 1,2-didecanoylglycerol (n = 5), caused a dose-dependent stimulation of oxytocin secretion in the presence of a calcium ionophore (A23187; 0·2 μmol/l). Phospholipase C (PLC; 50–250 units/l) also caused a dose-dependent stimulation of oxytocin secretion by luteal slices. Phospholipase C-stimulated oxytocin secretion was potentiated by the addition of an inhibitor of diacylglycerol kinase (R59 022; n = 4). These data suggest that the activation of protein kinase C has a role in the stimulation of luteal oxytocin secretion. The results are also consistent with the involvement of protein kinase C in PLC-stimulated oxytocin secretion. The cyclic AMP second messenger system does not appear to be involved in the control of oxytocin secretion by the corpus luteum. Journal of Endocrinology (1990) 124, 225–232

Rat histidine decarboxylase promoter is regulated by gastrin through a protein kinase C pathway

1996 ◽  
Vol 270 (4) ◽  
pp. G619-G633 ◽  
Author(s):  
M. Hocker ◽  
Z. Zhang ◽  
D. A. Fenstermacher ◽  
S. Tagerud ◽  
M. Chulak ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Time Course ◽  
Histidine Decarboxylase ◽  
Peptide Hormone ◽  
Direct Stimulation ◽  
Gastric Glands ◽  
Kinase C ◽  
Translational Start ◽  
Stimulation Of

The enzyme L-histidine decarboxylase (HDC; EC 4.1.1.22), which converts L-histidine to histamine, plays a key role in the regulation of acid secretion. In the rat and human stomach, the peptide hormone gastrin appears to be one of the main regulators of HDC expression. In rats, marked elevation of gastric HDC mRNA abundance was observed within 12 h after induction of hypergastrinemia by a single injection of the proton-pump blocker omeprazole. In situ hybridization revealed that HDC expression occurred in the basal third of gastric glands where enterochromaffin-like cells are localized. To study the regulation of HDC gene transcription, 1,291 nucleotides of the 5'-flanking region of the rat HDC gene and the noncoding portion of exon 1 were cloned and sequenced. Gastrin and cholecystokinin (CCK) octapeptide equipotently stimulated the transcriptional activity of the rat HDC promoter three- to fourfold, and deletion analysis revealed the presence of a gastrin response element within 201 nucleotides upstream of the translational start site. Time-course studies revealed maximal activation of the HDC promoter after 12-36 h. Direct stimulation of protein kinase C (PKC) with the phorbol ester phorbol 12-myristate 13-acetate (PMA) substantially elevated rat HDC promoter activity, whereas induction of Ca2+ -dependent signaling pathways with thapsigargin was without effect. Downregulation or blockade of PKC abolished the effects of gastrin and PMA on the HDC promoter. These data indicate that stimulation of the CCK-B/gastrin receptor activates the rat HDC promoter in a time- and dose-dependent fashion and that this effect is primarily mediated via a PKC-dependent signaling pathway. Use of HDC as a model gene will allow further investigation of the intracellular pathways that are involved in gastrin-dependent gene regulation.

Leptin Constrains Phospholipase C-Protein Kinase C-Induced Insulin Secretion via a Phosphatidylinositol 3-Kinase-Dependent Pathway

2003 ◽  
Vol 228 (2) ◽  
pp. 175-182 ◽  
Author(s):  
Joo-Won Lee ◽  
Andrew G. Swick ◽  
Dale R. Romsos
Keyword(s):  
Protein Kinase C ◽  
Insulin Secretion ◽  
Protein Kinase ◽  
Phospholipase C ◽  
Phosphatidylinositol 3 Kinase ◽  
C Protein ◽  
Kinase C ◽  
Pka Pathway ◽  
Stimulation Of ◽  
Phosphatidylinositol 3

Leptin-deficient Lepob/Lepob mice hypersecrete insulin in response to acetylcholine stimulation of the phospholipase C-protein kinase C (PLC-PKC) pathway, and leptin constrains this hypersecretion. Leptin has been reported to activate phosphatidylinositol 3-kinase (PI 3-K) and subsequently phosphodiesterase (PDE) to impair protein kinase A (PKA)-induced insulin secretion from cultured islets of neonatal rats. We determined if PKA-induced insulin secretion was also hyperresponsive in Islets from Lepob/Lepob mice, and if leptin impaired this pathway in islets from these mice. Additionally, the possible role for PI 3-K and PDE in leptin-induced control of acetylcholine-induced insulin secretion was examined. Stimulation of Insulin secretion with GLP-1, forskolin (an activator of adenylyl cyclase), or IBMX (an inhibitor of PDE) did not cause hypersecretion of insulin from islets of young Lepob/Lepob mice, and leptin did not inhibit GLP-1-induced insulin secretion from islets of these mice. Inhibition of PDE with IBMX also did not block leptin-induced inhibition of acetylcholine-mediated insulin secretion from islets of Lepob/Lepob mice. But, preincubation of islets with wortmannin, an Inhibitor of PI 3-K activity, blocked the ability of leptin to constrain acetylcholine-induced insulin secretion from islets of Lepob/Lepob mice. We conclude that the capacity of the PKA pathway to stimulate insulin secretion is not increased in islets from young Lepob/Lepob mice, and that leptin does not regulate this pathway in islets from mice. Leptin may stimulate PI 3-K to constrain PLC-PKC-induced insulin secretion from Islets of Lepob/Lepob mice.

Inhibition of voltage-gated K+ current in rat intrapulmonary arterial myocytes by endothelin-1

1998 ◽  
Vol 274 (5) ◽  
pp. L842-L853 ◽  
Author(s):  
Larissa A. Shimoda ◽  
J. T. Sylvester ◽  
James S. K. Sham
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Phospholipase C ◽  
Vascular Reactivity ◽  
Signal Transduction Pathway ◽  
Patch Clamp Technique ◽  
Arterial Smooth Muscle ◽  
Kinase C ◽  
Gf 109203X

Although endothelin (ET)-1 is an important regulator of pulmonary vascular tone, little is known about the mechanisms by which ET-1 causes contraction in this tissue. Using the whole cell patch-clamp technique in rat intrapulmonary arterial smooth muscle cells, we found that ET-1 and the voltage-dependent K+(KV)-channel antagonist 4-aminopyridine, but not the Ca2+-activated K+-channel antagonist charybdotoxin (ChTX), caused membrane depolarization. In the presence of 100 nM ChTX, ET-1 (10−10to 10−7 M) caused a concentration-dependent inhibition of K+ current (56.2 ± 3.8% at 10−7 M) and increased the rate of current inactivation. These effects of ET-1 on K+ current were markedly reduced by inhibitors of protein kinase C (staurosporine and GF 109203X) and phospholipase C (U-73122) or under Ca2+-free conditions and were mimicked by activators of protein kinase C (phorbol 12-myristate 13-actetate and 1,2-dioctanoyl- sn-glycerol). These data suggest that ET-1 modulated pulmonary vascular reactivity by depolarizing pulmonary arterial smooth muscle, due in part to the inhibition of KV current that occurred via activation of the phospholipase C-protein kinase C signal transduction pathway.

Extracellular Ca2+ decreases chloride reabsorption in rat CTAL by inhibiting cAMP pathway

1998 ◽  
Vol 275 (2) ◽  
pp. F198-F203 ◽  
Author(s):  
Marie Céleste De Jesus Ferreira ◽  
Claire Bailly
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Rat Kidney ◽  
Inhibitory Effect ◽  
Phospholipase A ◽  
Thick Ascending Limb ◽  
Time Control ◽  
Camp Pathway ◽  
Kinase C ◽  
Gf 109203X

The effect of activation of the Ca2+-sensing receptor on net Cl flux ( J Cl) has been investigated on microperfused cortical (C) thick ascending limb (TAL) from rat kidney. Increasing bath Ca2+ from 0.5 to 3 mM or adding 200 μM of the specific Ca2+-sensing receptor agonist neomycin reduced basal as well as antidiuretic hormone (ADH)-stimulated J Cl by 27.7 ± 5.0% and 25.9 ± 4.1%, respectively. J Cl remained unchanged in time control tubules. The effect of neomycin/Ca2+ on J Cl was blocked by two protein kinase A inhibitors, H-9 or H-89, but not by a protein kinase C inhibitor, GF-109203X, regardless of whether ADH was present or not. Moreover, H-89 decreased basal J Cl and prevented a further effect of 3 mM Ca2+. When J Cl was increased by 8-bromo-cAMP plus IBMX, no effect of 3 mM Ca2+ was observed. Inhibitors of phospholipase A2 and cytochrome P-450 monooxygenase failed to modify the effect of 3 mM Ca2+, although these agents dampened significantly the inhibitory effect of bradykinin on medullary TAL. We conclude that extracellular Ca2+ decreases basal and ADH-stimulated Cl reabsorption in CTAL by inhibiting the cAMP pathway, independently of protein kinase C or phospholipase A2 stimulation.

scholarly journals G-protein βγ subunits antagonize protein kinase C-dependent phosphorylation and inhibition of phospholipase C-β1

1997 ◽  
Vol 326 (3) ◽  
pp. 701-707 ◽  
Author(s):  
Irene LITOSCH
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phospholipase C ◽  
G Protein ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Negative Feedback Regulation ◽  
Kinase C ◽  
Stimulation Of

Protein kinase C (PKC) isoforms phosphorylated phospholipase C-β1 (PLC-β1) in vitro as follows: PKCα ≫ PKCϵ; not PKCζ. PLC-β3 was not phosphorylated by PKCα. G-protein βγ subunits inhibited the PKCα phosphorylation of PLC-β1 in a concentration-dependent manner. Half-maximal inhibition occurred with 500 nM βγ. G-protein βγ subunits also antagonized the PKCα-mediated inhibition of PLC-β1 enzymic activity. PKCα, in turn, inhibited the stimulation of PLC-β1 activity by βγ. There was little effect of PKCα on the stimulation of PLC-β1 by αq/11–guanosine 5′[γ-thio]triphosphate (GTP[S]). These findings demonstrate that G protein βγ subunits antagonize PKCα regulation of PLC-β1. Thus βγ subunits might have a role in modulating the negative feedback regulation of this signalling system by PKC.

Stimulation of transient elevations in cytosolic Ca2+ is related to inhibition of Pi transport in OK cells

1990 ◽  
Vol 259 (3) ◽  
pp. F485-F493 ◽  
Author(s):  
A. Miyauchi ◽  
V. Dobre ◽  
M. Rickmeyer ◽  
J. Cole ◽  
L. Forte ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Parathyroid Hormone ◽  
Protein Kinase ◽  
Phospholipase C ◽  
Cytosolic Calcium ◽  
Wild Type ◽  
Kinase C ◽  
Pi Transport ◽  
Sodium Dependent ◽  
Stimulation Of

Stimulation of changes in cytosolic free calcium by parathyroid hormone was determined in three opossum kidney (OK) cell types, OK wild-type, OKP clone, and OKH clone. All three types of OK cells express parathyroid hormone (PTH)-sensitive adenylate cyclase and adenosine 3',5'-cyclic monophosphate (cAMP) production. However, only the OK wild-type and the OKP clone respond to PTH with inhibition of sodium-dependent Pi transport and transient increase in cytosolic calcium. Characterization of the increases in cytosolic calcium in the wild-type and OKP clones revealed they were due in part to stimulation of Ca2+ release from intracellular stores, probably by inositol 1,4,5-trisphosphate (IP3), which was stimulated by PTH. PTH-stimulated Ca2+ transients were also inhibited by protein kinase C activation. These data are compatible with PTH receptor-mediated phospholipase C activation and its feedback inhibition by protein kinase C. The OKH cells demonstrated a slow increase in cytosolic calcium when stimulated by cyclic nucleotides but no evidence for PTH stimulation of Ca2+ release from intracellular stores. Thus the absence of an inhibitory response of sodium-dependent Pi transport to PTH in the OKH cells is associated with the absence of the rapid transient elevations of cytosolic Ca2+ such as those produced by IP3 production. These data suggest an important cooperative role for cAMP and the phospholipase C-stimulated Ca2(+)-protein kinase C message system in the regulation of Pi transport.

scholarly journals Direct stimulation of protein kinase C by arachidonate is associated with platelet activation.

1987 ◽  
Vol 18 (2) ◽  
pp. 138-141
Author(s):  
Masakatsu NISHIKAWA ◽  
Yasuhiro UEMURA ◽  
Hideo WADA ◽  
Katsumi DEGUCHI ◽  
Shigeru SHIRAKAWA
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Platelet Activation ◽  
Direct Stimulation ◽  
Kinase C ◽  
Stimulation Of
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