A role for protein kinase C in bradykinin-mediated activation of renal pelvic sensory receptors

1995 ◽  
Vol 269 (2) ◽  
pp. R331-R338 ◽  
Author(s):  
U. C. Kopp ◽  
L. A. Smith
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Feedback Inhibition ◽  
Normal Diet ◽  
Sensory Receptors ◽  
Renal Nerve ◽  
Kinase C ◽  
Renal Nerve Activity ◽  
Pelvic Perfusion ◽  
20 Nm

In anesthetized rats, activation of renal pelvic sensory receptors by bradykinin results in an increase in afferent renal nerve activity (ARNA) that is dependent on intact renal prostaglandin synthesis. Since bradykinin is a known activator of the phosphoinositide system, we examined whether the increase in ARNA produced by bradykinin involved activation of protein kinase C (PKC). Renal pelvic perfusion with the phorbol ester 4 beta-phorbol 12,13-dibutyrate (PDBu, 1 microM) increased ARNA (31 +/- 3%, P < 0.01) in rats fed a normal diet but not in rats fed an essential fatty acid-deficient (EFAD) diet. Renal pelvic perfusion with the PKC inhibitors calphostin C (1 microM), staurosporine (20 nM), and H-7 (40 microM) reduced the ARNA responses to bradykinin (20 microM) by 69 +/- 10, 76 +/- 10, and 77 +/- 10%, respectively (all P < 0.01). Pretreatment with PDBu (1 microM), known to cause a feedback inhibition of bradykinin-mediated activation of the phosphoinositide system, reduced the ARNA response to bradykinin by 73 +/- 6% (P < 0.01). Pretreatment with 4 alpha-phorbol 12,13-didecanoate was without effect. These findings suggest that activation of PKC contributes importantly to the activation of renal pelvic sensory receptors by bradykinin, likely via release of arachidonic acid.

Activation of renal mechanosensitive neurons involves bradykinin, protein kinase C, PGE2, and substance P

2000 ◽  
Vol 278 (4) ◽  
pp. R937-R946 ◽  
Author(s):  
Ulla C. Kopp ◽  
Donna M. Farley ◽  
Michael Z. Cicha ◽  
Lori A. Smith
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Substance P ◽  
Receptor Antagonist ◽  
Renal Nerve ◽  
Kinase C ◽  
Renal Nerve Activity ◽  
Substance P Receptor ◽  
Pelvic Perfusion ◽  
Pelvic Pressure

Increased renal pelvic pressure or bradykinin increases afferent renal nerve activity (ARNA) via PGE2-induced release of substance P. Protein kinase C (PKC) activation increases ARNA, and PKC inhibition blocks the ARNA response to bradykinin. We now examined whether bradykinin mediates the ARNA response to increased renal pelvic pressure by activating PKC. In anesthetized rats, the ARNA responses to increased renal pelvic pressure were blocked by renal pelvic perfusion with the bradykinin B2-receptor antagonist HOE 140 and the PKC inhibitor calphostin C by 76 ± 8% ( P < 0.02) and 81 ± 5% ( P < 0.01), respectively. Renal pelvic perfusion with 4β-phorbol 12,13-dibutyrate (PDBu) to activate PKC increased ARNA 27 ± 4% and renal pelvic release of PGE2 from 500 ± 59 to 1,113 ± 183 pg/min and substance P from 10 ± 2 to 30 ± 2 pg/min (all P < 0.01). Indomethacin abolished the increases in substance P release and ARNA. The PDBu-mediated increase in ARNA was also abolished by the substance P-receptor antagonist RP 67580. We conclude that bradykinin contributes to the activation of renal pelvic mechanosensitive neurons by activating PKC. PKC increases ARNA via a PGE2-induced release of substance P.

scholarly journals Protein kinase C activity is not involved in N-formylmethionyl-leucyl-phenylalanine-induced phospholipase D activation in human neutrophils, but is essential for concomitant NADPH oxidase activation: studies with a staurosporine analogue with improved selectivity for protein kinase C

1993 ◽  
Vol 292 (3) ◽  
pp. 781-785 ◽  
Author(s):  
G C Kessels ◽  
K H Krause ◽  
A J Verhoeven
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Nadph Oxidase ◽  
Phospholipase D ◽  
Respiratory Burst ◽  
Feedback Inhibition ◽  
Human Neutrophils ◽  
Kinase C ◽  
Pkc Activation

Stimulation of human neutrophils by the receptor agonist N-formylmethionyl-leucyl-phenylalanine (fMLP) results in a respiratory burst, catalysed by an NADPH oxidase. Concomitantly, phospholipase D (PLD) is activated. To investigate the role of protein kinase C (PKC) in these neutrophil responses, we have compared the effects of staurosporine and a structural analogue of staurosporine (cgp41251), that reflects a higher selectivity towards PKC [Meyer, Regenass, Fabbro, Alteri, Rösel, Müller, Caravatti and Matter (1989) Int. J. Cancer 43, 851-856]. Both staurosporine and cgp41251 dose-dependently inhibited the production of superoxide induced by phorbol 12-myristate 13-acetate (PMA). Both compounds also caused inhibition of the fMLP-induced respiratory burst, but with a lower efficacy during the initiation phase of this response. This latter observation cannot be taken as evidence against PKC involvement in the activation of the respiratory burst, because pretreatment of neutrophils with ionomycin before PMA stimulation also results in a lower efficacy of inhibition. Activation of PLD by fMLP was enhanced in the presence of staurosporine, but not in the presence of cgp41251. Enhancement of PLD activation was also observed in the presence of H-89, an inhibitor of cyclic-AMP-dependent protein kinase (PKA). Both staurosporine and H-89 reversed the dibutyryl-cyclic-AMP-induced inhibition of PLD activation, whereas cgp41251 was without effect. These results indicate that the potentiating effect of staurosporine on PLD activation induced by fMLP does not reflect a feedback inhibition by PKC activation, but instead a feedback inhibition by PKC activation. Taken together, our results indicate that in human neutrophils: (i) PKC activity is not essential for fMLP-induced activation of PLD; (ii) PKC activity does play an essential role in the activation of the respiratory burst by fMLP, other than mediating or modulating PLD activation; (iii) there exists a negative-feedback mechanism on fMLP-induced PLD activation by concomitant activation of PKA.

Bradykinin-mediated activation of renal sensory neurons due to prostaglandin-dependent release of substance P

1997 ◽  
Vol 272 (6) ◽  
pp. R2009-R2016 ◽  
Author(s):  
U. C. Kopp ◽  
D. M. Farley ◽  
L. A. Smith
Keyword(s):  
Substance P ◽  
Sensory Receptors ◽  
Nerve Activity ◽  
Renal Nerve ◽  
P Release ◽  
Renal Nerve Activity ◽  
Substance P Receptor ◽  
Pelvic Perfusion ◽  
Substance P Release ◽  
Substance P Receptors

In anesthetized rats, renal pelvic administration of bradykinin results in a prostaglandin (PG)-dependent increase in afferent renal nerve activity (ARNA). We now measured renal pelvic release of PGE and substance P during renal pelvic administration of bradykinin. Bradykinin increased ARNA and renal pelvic release of PGE by 497 +/- 252 pg/min and substance P. by 10.7 +/- 7.2 pg/min. Renal pelvic perfusion with indomethacin abolished the bradykinin-mediated increase in ARNA and reduced renal pelvic release of PGE and substance P by 76 +/- 11 and 72 +/- 8%, respectively. To examine whether the increased substance P release contributed to bradykinin-mediated activation of renal sensory receptors, renal pelvis was perfused with the substance P-receptor antagonists CP-96,345, CP-99,994, or RP-67580. The ARNA response to bradykinin was reduced 73 +/- 11, 55 +/- 12, and 64 +/- 10% by CP-96,345, CP-99,994, and RP-67580, respectively. The inactive enantiomers CP-96,344 and RP-68651 had no effect. These data suggest that bradykinin increases renal pelvic release of PGE, which facilitates the release of substance P, which in turn stimulates substance P receptors. Thus the ARNA response to bradykinin is largely mediated by activation of substance P receptors.

Inhibitory renorenal reflexes: a role for renal prostaglandins in activation of renal sensory receptors

1991 ◽  
Vol 261 (6) ◽  
pp. R1513-R1521 ◽  
Author(s):  
U. C. Kopp ◽  
L. A. Smith
Keyword(s):  
Chemical Activation ◽  
Urinary Sodium Excretion ◽  
Reflex Response ◽  
Sensory Receptor ◽  
Chemical Stimulus ◽  
Sensory Receptors ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Renal Nerve Activity ◽  
Pelvic Perfusion

In anesthetized rats, activation of renal sensory receptors with a mechanical stimulus (increased ureteral pressure) and a chemical stimulus (renal pelvic perfusion with 0.9 M NaCl) results in an increase in ipsilateral afferent renal nerve activity and a reflex increase in contralateral urine flow rate and urinary sodium excretion, i.e., a contralateral inhibitory renorenal reflex. Because both interventions are known to increase renal prostaglandin (PG) synthesis, we examined whether renal PGs were involved in the renorenal reflex response to renal sensory receptor stimulation. In the first part, mechanical and chemical activation of renal sensory receptors was performed in the absence and presence of renal pelvic perfusion with indomethacin or meclofenamate (0.2 micrograms/min). Indomethacin inhibited the ipsilateral afferent renal nerve activity response to increased ureteral pressure (7 +/- 2 vs. 38 +/- 10%, P less than 0.01) and renal pelvic perfusion with 0.9 M NaCl (3 +/- 3 vs. 28 +/- 5%, P less than 0.01) and the contralateral diuretic and natriuretic responses in the absence of any renal hemodynamic changes. Similar effects were produced by meclofenamate. In the second part, mechanical and chemical activation of renal sensory receptors was performed in the presence of renal pelvic perfusion with vehicle, indomethacin, and indomethacin plus PGE2 (20 micrograms/min). Addition of PGE2 to the renal pelvic perfusate in indomethacin-treated kidneys restored the responses to mechanical and chemical activation of renal sensory receptors to levels not different from their pre-indomethacin control values. We conclude that PGs in the renal pelvic area are involved in inhibitory renorenal reflex responses to mechanical and chemical activation of renal sensory receptors.

scholarly journals Preferential release of catecholamine from permeabilized PC12 cells by α- and β-type protein kinase C subspecies

1991 ◽  
Vol 280 (1) ◽  
pp. 65-69 ◽  
Author(s):  
H Ben-Shlomo ◽  
O Sigmund ◽  
S Stabel ◽  
N Reiss ◽  
Z Naor
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Pc12 Cells ◽  
Neurotransmitter Release ◽  
Kinase C ◽  
Insertion Method ◽  
Group A ◽  
Pkc Alpha ◽  
Neuronal Functions ◽  
20 Nm

Protein kinase C (PKC) is now recognized as comprising two groups of closely related subspecies. The PKC gamma enzyme is apparently present only in central nervous tissues, and hence was expected to participate in neurotransmitter release. We have utilized a ‘depletion-insertion’ method to identify the PKCs participating in the exocytotic response. PC12 cells were ‘down-regulated’ by prior treatment (24 h) with phorbol 12-myristate 13-acetate (PMA; 1 microM), which nearly abolished endogenous PKC activity. Down-regulated PC12 cells were loaded with [3H]dopamine, permeabilized with digitonin, and recombinant or purified PKCs were inserted and activated with a low dose of PMA (20 nM). Among group A PKCs, PKC alpha was the most effective activator of [3H]dopamine release (215%), followed by beta II (185%) and beta I (150%). PKC gamma had no consistent effect on neurotransmitter release. PC12 cells express PKC alpha and PKC beta, but not PKC gamma, as revealed by Northern-blot analysis. We therefore postulate that PKC alpha and PKC beta participate in neurotransmitter release, whereas PKC gamma might be involved in other neuronal functions.

scholarly journals Phorbol 12-myristate 13-acetate activates an electrogenic H+-conducting pathway in the membrane of neutrophils

1992 ◽  
Vol 281 (3) ◽  
pp. 697-701 ◽  
Author(s):  
A Kapus ◽  
K Szászi ◽  
E Ligeti
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Nadph Oxidase ◽  
Phorbol Esters ◽  
Charge Compensation ◽  
Kinase C ◽  
Low Concentrations ◽  
Conducting Pathway ◽  
20 Nm ◽  
Stimulation Of

The mode of activation of an H(+)-conducting pathway present in the membrane of neutrophils was investigated. (1) Resting neutrophils released protons through an electrogenic Cd(2+)-inhibitable (K0.5 approximately 20 microM) route when a pH gradient and appropriate charge compensation was provided. (2) The rate of H+ efflux was stimulated over 2.5-fold by 4 beta-phorbol 12-myristate 13-acetate (PMA; K0.5 approximately 0.7 nM) or by 4 beta-phorbol 12,13-dibutyrate (K0.5 approximately 20 nM) even when the NADPH oxidase was blocked by p-chloromercuribenzoate. (3) Staurosporine inhibited the effect of PMA. (4) The H+ egress was not enhanced by 4 alpha-phorbol 12,13-didecanoate. (5) Low concentrations of Cd2+ (less than 40 microM) inhibited the H+ flux without influencing the oxidase. The results raise the possibility that protein kinase C could be involved in the activation of an electrogenic H(+)-conducting pathway in the membrane of neutrophils. The activation of this route by phorbol esters seems to be independent of the stimulation of NADPH oxidase.

Role of prostaglandins in renal sensory receptor activation by substance P and bradykinin

1993 ◽  
Vol 265 (3) ◽  
pp. R544-R551 ◽  
Author(s):  
U. C. Kopp ◽  
L. A. Smith
Keyword(s):  
Substance P ◽  
Urinary Sodium Excretion ◽  
Receptor Activation ◽  
Prostaglandin Synthesis ◽  
Sensory Receptor ◽  
Sensory Receptors ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Renal Nerve Activity ◽  
Pelvic Perfusion

In anesthetized rats increasing ureteral pressure results in an increase in ipsilateral afferent renal nerve activity and a reflex increase in contralateral urine flow rate and urinary sodium excretion that is dependent on intact prostaglandin synthesis. Activation of renal pelvic substance P receptors contributes to the renorenal reflex responses to increased ureteral pressure. Because these data suggested that renal sensory receptors could be activated by both prostaglandins and substance P we examined whether activation of renal sensory receptors by substance P was dependent on intact prostaglandin synthesis. The renal pelvis was perfused with capsaicin, 2.5 micrograms/ml, or substance P, 4 micrograms/ml, before and during renal pelvic perfusion with the prostaglandin synthesis inhibitor indomethacin, 50 micrograms/ml. Indomethacin reduced the peak ipsilateral afferent renal nerve activity responses to capsaicin and substance P by 83 +/- 15% and 81 +/- 8%, respectively, as well as the contralateral diuretic and natriuretic responses. We also examined the effects of renal pelvic administration of indomethacin on the responses to renal pelvic perfusion with bradykinin. Bradykinin, 20 micrograms/ml, increased peak ipsilateral afferent renal nerve activity by 197 +/- 47% and contralateral urine flow rate and urinary sodium excretion by 31 +/- 6 and 20 +/- 6%, respectively. Indomethacin reduced the ipsilateral afferent renal nerve activity response by 76 +/- 9% and abolished the contralateral diuretic and natriuretic responses to bradykinin. We conclude that renal sensory receptor activation by capsaicin, substance P, and bradykinin is dependent on intact renal prostaglandin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Influence of staurosporine on glucose-mediated and glucose-conditioned insulin secretion

1991 ◽  
Vol 279 (3) ◽  
pp. 807-813 ◽  
Author(s):  
W S Zawalich ◽  
K C Zawalich ◽  
S Ganesan ◽  
R Calle ◽  
H Rasmussen
Keyword(s):  
Protein Kinase C ◽  
Insulin Secretion ◽  
Protein Kinase ◽  
Glucose Metabolism ◽  
Time Course ◽  
Second Phase ◽  
Kinase C ◽  
Marked Inhibition ◽  
20 Nm ◽  
Pkc Activation

The effect of staurosporine, a putative inhibitor of protein kinase C (PKC), on insulin secretion induced by glucose and 4-methyl-2-oxopentanoate (KIC) was examined. In addition, the effects of staurosporine on the actions of other agonists, for which glucose acts as a conditional modifier, were also examined. At 20 nM, staurosporine caused a marked inhibition of second-phase insulin secretion, whether it was stimulated by 10 mM- or 20 mM-glucose, by 15 mM-KIC, or by carbachol or tolbutamide in islets co-perifused with 7.0 mM-glucose. In each case, the second-phase secretory response was inhibited by 70-85%. In contrast, in all cases there was no effect of staurosporine on the magnitude of the first phase of insulin secretion, nor on the time course of first-phase secretion, except when glucose alone was the secretagogue. With either 10 mM- or 20 mM-glucose, the peak of the first phase of insulin secretion was delayed. Staurosporine does not alter glucose metabolism, or the ability of glucose to activate phosphoinositide hydrolysis or to cause the translocation of alpha-PKC to the membrane. These findings support the concept that PKC activation plays an important role in fuel-induced or fuel-conditioned insulin secretion.

scholarly journals Different isozymes of protein kinase C mediate feedback inhibition of phospholipase C and stimulatory signals for exocytosis in rat RBL-2H3 cells.

1993 ◽  
Vol 268 (4) ◽  
pp. 2280-2283 ◽  
Author(s):  
K. Ozawa ◽  
K. Yamada ◽  
M.G. Kazanietz ◽  
P.M. Blumberg ◽  
M.A. Beaven
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phospholipase C ◽  
Feedback Inhibition ◽  
Kinase C
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