| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Physiology, College of Medicine, and McKnight Brain Institute, University of Florida, Gainesville, Florida 32610
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
It was previously
determined that ANG II and phorbol esters inhibit Kv current in neurons
cultured from newborn rat hypothalamus and brain stem in a protein
kinase C (PKC)- and Ca2+-dependent manner. Here, we have
further defined this signaling pathway by investigating the roles of
"physiological" activators of PKC and different PKC isozymes. The
cell-permeable PKC activators, diacylglycerol (DAG) analogs
1,2-dioctanoyl-sn-glycerol (1 µmol/l, n = 7) and 1-oleoyl-2-acetyl-sn-glycerol (1 µmol/l,
n = 6), mimicked the effect of ANG II and inhibited Kv
current. These effects were abolished by the PKC inhibitor
chelerythrine (1 µmol/l, n = 5) or by chelation of
internal Ca2+ (n = 8). PKC antisense (AS)
oligodeoxynucleotides (2 µmol/l) against Ca2+-dependent
PKC isoforms were applied to the neurons to manipulate the endogenous
levels of PKC. PKC-
-AS (n = 4) treatment abolished the inhibitory effects of ANG II and
1-oleoyl-2-acetyl-sn-glycerol on Kv current, whereas
PKC-
-AS (n = 4) and PKC-
-AS (n = 4) did not. These results suggest that the angiotensin type 1 receptor-mediated effects of ANG II on neuronal Kv current involve
activation of PKC-.
antisense; calcium; angiotensin type 1 receptor
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
MAMMALIAN BRAIN CONTAINS SPECIFIC angiotensin type 1 (AT1) receptors that are localized mainly in specific areas within the hypothalamus and brain stem (12, 27). Some of these areas lie outside the blood-brain barrier and sense circulating ANG II. ANG II acts at these receptors located on neurons to stimulate increases in blood pressure, arginine vasopressin release, salt appetite, and drinking behavior, effects that participate in the modulatory role of this peptide on extracellular fluid volume and cardiovascular hemodynamics (26, 33). In accordance with these physiological studies, it has been determined that ANG II elicits AT1 receptor-mediated increases in neuronal firing rate in the paraventricular nucleus, the subfornical organ, the supraoptic nucleus, and the rostral ventrolateral medulla, brain areas that are involved in cardiovascular regulation (2, 19, 29, 38). Changes in neuronal activity are governed by alterations in membrane currents through direct receptor-ion channel interactions or through receptor-mediated changes in intracellular messengers. Despite these well-documented physiological actions of ANG II in the brain, the mechanisms through which this peptide alters neuronal activity are not well established. An understanding of these mechanisms is crucial, since changes in neuronal activity induced by ANG II will ultimately lead to the above alterations in cardiovascular hemodynamics induced by this peptide.
Our group has utilized cultured neurons prepared from the hypothalamus
and brain stem of newborn rats to investigate the mechanisms of
AT1 receptor-mediated changes in neuronal activity and the intracellular signaling molecules that are involved (10, 29, 33,
35, 38, 39, 42). We have determined that activation of
AT1 receptors in cultured neurons increases neuronal firing rate and that this involves inhibition of neuronal delayed rectifier K+ (Kv) current and transient (A-type) K+
currents. The inhibitory effects of ANG II on Kv current involve a
signaling cascade revolving around Gq/11 protein,
stimulation of phosphoinositide hydrolysis, an increase in
intracellular free Ca2+ concentration, activation of
protein kinase C (PKC), and modulation of Kv2.2. The major goals of the
present study were to investigate the role of diacylglycerol (DAG) and
determine which PKC isozyme is involved in this signaling pathway. This
is important, because ANG II exerts a variety of AT1
receptor-mediated effects in neurons, many of which involve activation
of PKC (29). For example, aside from the inhibition of Kv
current, ANG II increases the phosphorylation of myristilated
alanine-rich C kinase substrate protein via PKC- (20)
and stimulates Fos-regulating kinase (13). Thus it is possible that these actions of ANG II involved different PKC isozymes, allowing this peptide to have differential effects on specific cellular
responses. Furthermore, it is well known that the activity of
K+ channels can be modulated by phosphorylation or
dephosphorylation (17). One of our future goals is to
determine whether ANG II elicits inhibition of Kv current via
PKC-mediated phosphorylation of Kv2.2; to accomplish this goal, an
understanding of which isozyme of PKC is involved is essential.
The data presented here show that DAG as well as the
Ca2+-dependent PKC- are involved in the regulation of
neuronal Kv current, changes that will ultimately lead to altered
cardiovascular function. This is the first demonstration of a specific
PKC isozyme that is responsible for modulating ANG II-induced changes
in neuronal Kv current. The identification of PKC- as a key
intermediate will allow for more discrete analysis of the role of this
serine/threonine kinase in the modulation of Kv channel activity.
| |
METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Materials. Newborn Sprague-Dawley rats were obtained from our breeding colony, which originated from Charles River Farms (Wilmington, MA). DMEM was obtained from GIBCO-BRL (Gaithersburg, MD). Losartan potassium was generously provided by William Henckler (Merck, Rahway, NJ). PD-123319 and calphostin were purchased from Research Biochemicals International (Natick, MA). Tetrodotoxin was purchased from Calbiochem (La Jolla, CA). U-73122, plasma-derived horse serum, ANG II, sodium GTP, HEPES, CdCl2, BSA, dipotassium ATP, and peroxidase-conjugated affinity-purified goat anti-rabbit IgG were purchased from Sigma Chemical (St. Louis, MO). PKC antibodies were purchased from Santa Cruz Biochemicals. All other chemicals were purchased from Fisher Scientific (Pittsburgh, PA) and were of analytic grade or higher.
Preparation of cultured neurons. Neuronal cocultures were prepared from the hypothalamus and brain stem of newborn Sprague-Dawley rats exactly as described previously (33). Cultures consist of 90% neurons and 10% astrocyte glia and microglia.
For the PKC antisense (AS) oligodeoxynucleotide experiments, PKC--AS, --AS, and --AS and PKC- sense (S) were dissolved in water to an initial concentration of 200 µM, as previously described by our research group (20). For each
transfection, 10 µl of AS solution combined with 5 µl of Lipofectin
reagent were added to the culture dish. Cells were incubated at 37°C
in a CO2 incubator for 24-72 h before use. During this
time, the medium was not changed, nor was the AS replenished at any
time. AS and S oligonucleotides for the PKC-, -, and - genes
(23) were synthesized in the DNA core facility of the
Interdisciplinary Center for Biotechnology Research, University of
Florida. The sequences of these primers are as follows
|
|
|
|
Electrophysiological recordings.
Kv current was recorded using the whole cell patch-clamp technique
(9). The superfusate solution contained (in mmol/l) 140 NaCl, 5.4 KCl, 2.0 CaCl2, 2.0 MgCl2, 0.3 NaH2PO4, 0.001 tetrodotoxin, 0.3 CdCl2, 0.001 PD-123319 (angiotensin type 2 receptor
antagonist), 10 HEPES, and 10 dextrose, with pH adjusted to 7.4 with
NaOH. The recording electrode had resistances of 2-4 M
when
filled with an internal pipette solution containing (in mmol/l) 140 KCl, 2 MgCl2, 4 ATP, 0.1 GTP, 10 dextrose, and 10 HEPES,
with pH adjusted to 7.2 with KOH.
80 to
+10 mV for 80 ms every 10 s. Under these recording conditions, Kv
current and a transient Kv (A-type) current were recorded. However,
because of normal cell-to-cell variation in the cultures, some neurons
contain Kv and A-type K+ currents while other cells may
have only one type of Kv current. For this reason, the current
measurements from which mean current densities were derived were made
50 ms after the initiation of the test pulse, at which time they
reflect only Kv current (9). Current density is reported
as picoamperes per picofaraday.
Values are means ± SE. Statistical significance was evaluated
with the use of a paired t-test and ANOVA. Differences were considered significant at P < 0.05.
Analysis of PKC-AS effectiveness. The presence of Ca2+-dependent PKC subunit isoforms was determined by Western blot analysis exactly as described previously (14, 42). Protein was extracted from triplicate culture dishes for each experimental data point. All lanes were loaded with the same amount of protein (20 µg).
| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Role of phospholipase C in ANG
II-mediated inhibition of neuronal Kv current.
Although it has been previously shown that ANG II-mediated inhibition
of neuronal Kv current was coupled to the AT1 receptor and
activation of Gq/11 (35), the role of
phospholipase C (PLC) has yet to be determined. In all the experiments
presented, Kv current was recorded in the presence of PD-123319 (1 µmol/l), a selective blocker of angiotensin type 2 receptors. Under
these recording conditions, ANG II (100 nmol/l) elicited a significant inhibitory effect on Kv current (Fig. 1).
The effect of ANG II was completely reversed by superfusion of the
AT1 receptor antagonist losartan (1 µmol/l; Fig.
2A; see Fig. 5). U-73122 has
recently been shown to be a specific PLC inhibitor (32).
When the neurons were pretreated with the PLC inhibitor U-73122 (1 µmol/l) for 15 min, the effect of ANG II was abolished. Therefore,
these data show that PLC is involved in the AT1
receptor-dependent inhibition of Kv current.
|
|
Effects of DAG analogs and intracellular
Ca2+ on neuronal
Kv current.
It was demonstrated in our previous studies that the AT1
receptor-mediated inhibition of neuronal Kv current involves a
signaling cascade that requires changes in intracellular free
Ca2+ concentration and activation of PKC (35).
However, there are no data that show that the inhibition of neuronal
K+ current is via activation of DAG and/or a specific PKC
isoform. Cell-permeable DAG analogs
1,2-dioctanoyl-sn-glycerol (1 µmol/l) and
1-oleoyl-2-acetyl-sn-glycerol (OAG, 1 µmol/l) were used to examine whether these agents produce effects similar to ANG II. Superfusion of 1,2-dioctanoyl-sn-glycerol (1 µmol/l,
n = 7) or OAG (1 µmol/l, n = 6)
inhibited Kv current (Fig. 2, B and C; see Fig.
5). Complete current-voltage relationships for the effects of ANG II or
OAG on Kv current are shown in Fig. 3.
The inactive DAG analog 1,3-dioctanoylglycerol (10 µmol/l,
n = 5) was without effect (Fig. 2D; see Fig.
5). Because DAG activates PKC, we tested the effects of OAG on Kv
current in the presence of the PKC blocker chelerythrine. Pretreatment
of neurons with chelerythrine (1 µmol/l) for 20 min completely
abolished the effect of OAG on Kv current (Figs.
4A and
5). Finally,
1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (10 mmol/l), a Ca2+ chelating agent, predissolved in pipette
solution, also abolished the effect of OAG on Kv current, indicating
the involvement of Ca2+ and/or a Ca2+-dependent
PKC isoform (Figs. 4B and 5).
|
|
|
Effect of PKC-AS oligodeoxynucleotides on
Kv current.
To determine which Ca2+-dependent isozyme of
PKC was responsible for the AT1 receptor-mediated effect of
ANG II and OAG on neuronal Kv current, PKC--AS, --AS, and --AS
were used to elicit the "knockdown" of PKC-, -, and -
protein to reduce the expression of the corresponding isozyme. We
previously used this technique to selectively reduce various PKC
isozymes (20). Western blot analysis using neurons that
were pretreated for 24 h with the various PKC-AS (2 µmol/l)
showed that the AS for each PKC isozyme only "knocked down" the
corresponding PKC protein while having no effect on the others; i.e.,
PKC--AS decreased the protein levels of PKC- and not - or -
(Fig. 6). Each PKC-AS
oligodeoxynucleotide reduced its target protein by ~60-70%.
Therefore, we used these AS constructs in electrophysiological
experiments. In the PKC--AS-pretreated neurons (24-72 h), the
inhibitory effects of ANG II and OAG on Kv current were abolished
(Figs. 7A,
8A, and
9). In neurons pretreated with PKC--AS or --AS, the effects of ANG II or OAG were still present and resembled control responses (Figs. 7, B and
C, 8, B and C, and 9). Furthermore, in
PKC--S-pretreated neurons as controls, in which PKC- isozyme
expression would be unaffected by the pretreatment, superfusion of ANG
II (100 nM) elicited a significant inhibitory effect on Kv current that
was reversed by losartan (1 µmol/l; Figs. 7D and 9). These
data suggest that PKC- plays a crucial role in the AT1
receptor-mediated inhibitory effect of ANG II on neuronal Kv current.
|
|
|
|
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Our previous data indicate that ANG II acting via AT1
receptors increases neuronal firing rate and reduces Kv and A-type
K+ currents (9, 33, 35, 38, 39, 42). One
signaling pathway that all the above effects of ANG II had in common
was the activation of PKC. However, there are no data that show that the inhibition of neuronal Kv current is dependent on the activation of
DAG and/or a specific PKC isoform. The data presented here clearly show
that PLC and DAG are involved in the regulation of neuronal Kv current,
since membrane-permeant forms of DAG inhibit Kv current in a manner
similar to ANG II (Figs. 1-5). The present studies also clearly
indicate that the Ca2+-dependent PKC- is also involved
in AT1 receptor- and DAG-mediated inhibition of neuronal Kv
current (Figs. 7-9). These conclusions are primarily based on the
fact that PKC-AS directed against the -isoform, and not the - or
-isoform, of PKC blocked the inhibitory effects of ANG II and DAG
analogs. This is an important finding, since it could be argued that
ANG II acts in a paracrine manner to release a substance that, in turn,
causes inhibition of Kv current in another neuron.
It is apparent from the results that the effects of ANG II on Kv
current were completely abolished by PKC--AS treatments, which,
according to Western blot analysis, reduced PKC- protein by only
60-70%. There may be a number of reasons for this discrepancy. The most obvious possibility is that the effects of the AS are heterogeneous, causing complete depletion of PKC- in some cells, along with abolition of electrophysiological responses, while only
reducing PKC- expression in other cell populations. Thus, by
analysis of PKC- levels in the whole dish, only an overall reduction
of this protein after AS treatment would be detected. Another
possibility is that the PKC--AS has selective actions on the active
and inactive pools of PKC present in these cells. For example, it may
completely deplete the activated PKC- that is required for signal
transduction and have minimal effects on the inactive pool of this
kinase. The result would be complete inhibition of ANG II effects on Kv
current but only an overall reduction in PKC- expression. This is,
of course, speculation, and analyses of PKC- activity would be
required to prove or disprove this idea.
The hormonal regulation of ion channels plays an important role in the second-to-second regulation of the brain. There is a great deal of evidence that phosphorylation and/or dephosphorylation of Kv channel proteins is important in the regulation of their activity (17). PKC has been shown to modulate in vitro neuronal K+ currents (5, 7, 11, 31). With the use of expression systems, Kv1.1, Kv1.2, Kv1.3, Kv1.5, and Kv3.1 channels were inhibited by PKC in a similar manner. Namely, current amplitudes are reduced irreversibly over a long time course with little or no change in kinetics (1, 3, 6, 8, 21, 22, 25, 38). Using cultured neurons and the Xenopus oocyte expression system, we recently showed that the AT1 receptor-mediated inhibition of neuronal Kv currents is due to inhibition of Kv2.2 (9). Therefore, considering the fact that ANG II stimulates PKC activity in cultured neurons, it is reasonable to speculate that the reduction in Kv current caused by ANG II is mediated via direct phosphorylation of Kv2.2 by PKC or indirectly by PKC phosphorylating an auxiliary protein in a signaling cascade.
A number of questions remain to be answered. For example, do the
observed changes in neuronal Kv current include direct channel phosphorylation by PKC, or are the effects of these serine/threonine kinases indirect and mediated via activation of other enzymes (e.g.,
tyrosine kinases) that subsequently modulate channel activity via
phosphorylation? The identification of PKC- as the PKC isozyme that
is responsible for mediating the inhibitory effects of ANG II on Kv
current will enable us to determine whether this serine/threonine kinase directly phosphorylates Kv2.2. There is evidence that PKC activates cAMP-dependent protein kinase (24, 28), protein tyrosine kinases (15, 30), mitogen-activated protein
kinases (16), and tyrosine phosphatase (4,
36), and one or more of these enzymes might link
AT1A receptors and PKC to the inhibition of Kv2.2. In light
of this, the tyrosine kinase inhibitor genistein attenuates the ANG
II-induced inhibition of neuronal Kv current (unpublished
observations). Finally, what is the physiological consequence between
ANG II-dependent inhibition of neuronal Kv current and the actions of
ANG II in the brain? We previously showed that AT1 receptor
activation increases neuronal firing rate and the release of
norepinephrine (29, 38). Thus it is tempting to speculate
that the reduction in Kv current caused by ANG II via PKC contributes
to the release of norepinephrine.
| |
ACKNOWLEDGEMENTS |
|---|
This work was supported by National Institutes of Health Grants HL-49130 and NS-19441.
| |
FOOTNOTES |
|---|
Address for reprint requests and other correspondence: C. H. Gelband, Dept. of Physiology, Box 100274, 1600 SW Archer Rd., Gainesville, FL 32610 (E-mail: gelband{at}phys.med.ufl.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 14 August 2000; accepted in final form 1 November 2000.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Aiyar, J,
Grissmer S,
and
Chandy KG.
Full-length and truncated Kv1.3 K+ channels are modulated by 5-HT1c receptor activation and independently by PKC.
Am J Physiol Cell Physiol
265:
C1571-C1578,
1993
2.
Ambuhl, P,
Felix D,
Imboden H,
Khosla MC,
and
Ferrario CM.
Effects of angiotensin analogs and angiotensin receptor antagonists on paraventricular neurones.
Regul Pept
38:
111-120,
1992[ISI][Medline].
3.
Attali, B,
Honore E,
Lesage F,
Lazdunski M,
and
Barhanin J.
Regulation of a major cloned voltage-gated K+ channel from human T lymphocytes.
FEBS Lett
303:
229-232,
1992[ISI][Medline].
4.
Catarsi, S,
and
Drapeau P.
Requirement for tyrosine phosphatase during serotonergic neuromodulation by protein kinase C.
J Neurosci
17:
5792-5797,
1997
5.
Chandy, KG,
and
Gutman GA.
Voltage-gated K+ channel genes.
In: Ligand- and Voltage-Gated Ion Channels, edited by North RA.. Boca Raton, FL: CRC, 1995, p. 1-71.
6.
Critz, SD,
Wible BA,
Lopez HS,
and
Brown AM.
Stable expression and regulation of a rat brain K+ channel.
J Neurochem
60:
1175-1178,
1993[ISI][Medline].
7.
Doerner, D,
Pitler T,
and
Alger BE.
Protein kinase C activators block specific calcium and potassium current components in isolated hippocampal neurons.
J Neurosci
8:
4069-4078,
1988[Abstract].
8.
Furukawa, Y,
Kim HN,
and
Kubo T.
Up- and down-modulation of a cloned Aplysia K+ channel (AKv1.1a) by the activators of protein kinase C.
Zool Sci
12:
35-44,
1995[ISI][Medline].
9.
Gelband, CH,
Warth JD,
Mason HS,
Zhu M,
Moore JM,
Kenyon JL,
Horowitz B,
and
Sumners C.
Angiotensin II type 1 receptor-mediated inhibition of K+ channel subunit Kv2.2 in brain stem and hypothalamic neurons.
Circ Res
84:
352-359,
1999
10.
Gelband, CH,
Zhu M,
Lu D,
Reagan LP,
Fluharty SJ,
Posner P,
Raizada MK,
and
Sumners C.
Functional interactions between neuronal AT1 and AT2 receptors.
Endocrinology
138:
2195-2198,
1997
11.
Grega, DS,
Werz MA,
and
MacDonald RL.
Forskolin and phorbol esters reduce the potassium conductance of mouse neurons in culture.
Science
16:
345-348,
1987.
12.
Hogarty, DC,
Speakman EA,
Puig V,
and
Phillips MI.
The role of angiotensin AT1 and AT2 receptors in the pressor, drinking and vasopressin responses to central angiotensin.
Brain Res
586:
289-294,
1992[ISI][Medline].
13.
Huang, XC,
Deng T,
and
Sumners C.
Angiotensin II stimulates activation of Fos-regulating kinase and c-Jun NH2-terminal kinase in neuronal cultures from rat brain.
Endocrinology
139:
245-251,
1998
14.
Huang, X-C,
Shenoy UV,
Richards EM,
and
Sumners C.
Modulation of angiotensin II type 2 receptor mRNA in rat hypothalamus and brainstem neuronal cultures by growth factors.
Mol Brain Res
47:
229-236,
1997[Medline].
15.
Huang, XY,
Morielli AD,
and
Peralta EG.
Tyrosine kinase-dependent suppression of a potassium channel by the G protein-coupled M1 muscarinic acetylcholine receptor.
Cell
75:
1145-1156,
1993[ISI][Medline].
16.
Lev, S,
Moreno H,
Martinez R,
Canoll P,
Peles E,
Musacchio JM,
Plowman GD,
Rudy B,
and
Schlessinger J.
Protein tyrosine kinase PYK2 involved in Ca2+-induced regulation of ion channel and MAP kinase functions.
Nature
376:
737-745,
1995[Medline].
17.
Levitan, IB.
Modulation of ion channels by protein phosphorylation and dephosphorylation.
Annu Rev Physiol
56:
193-212,
1994[ISI][Medline].
18.
Li, YW,
and
Guyenet PG.
Neuronal excitation by angiotensin II in the rostral ventrolateral medulla of the rat in vitro.
Am J Physiol Regulatory Integrative Comp Physiol
268:
R272-R277,
1995
19.
Li, Z,
and
Ferguson AV.
Angiotensin II responsiveness of rat paraventricular and subfornical organ neurons in vitro.
Neuroscience
55:
197-207,
1993[ISI][Medline].
20.
Lu, D,
Yang H,
Lenox RH,
and
Raizada MK.
Regulation of angiotensin II-induced neuromodulation by MARCKS in brain neurons.
J Cell Biol
142:
217-227,
1998
21.
Mason, HS,
Gelband CH,
Sumners C,
Horowitz B,
and
Kenyon JL.
Inhibition of Kv2.2 expressed in Xenopus laevis oocytes by angiotensin II and PKC (Abstract).
J Physiol (Lond)
509:
63P,
1998.
22.
Murakoshi, H,
Ishii K,
Nunoki K,
and
Taira N.
Receptor-mediated modulation of rat Kv1.2 in Xenopus oocytes.
Eur J Pharmacol
268:
451-454,
1994[ISI][Medline].
23.
Ono, Y,
Fujii T,
Igarashi K,
Kikkawa U,
Ogita K,
and
Nishizuka Y.
Nucleotide sequences of cDNAs for and subspecies of rat brain protein kinase C.
Nucleic Acids Res
16:
5199-200,
1988
24.
Payet, MD,
and
Dupuis G.
Dual regulation of the n type K+ channel in Jurkat T lymphocytes by protein kinases A and C.
J Biol Chem
267:
18270-18273,
1992
25.
Peretz, T,
Levin G,
Moran O,
Thornhill WB,
Chikvashili D,
and
Lotan I.
Modulation by protein kinase C activation of rat brain delayed-rectifier K+ channel expressed in Xenopus oocytes.
FEBS Lett
381:
71-76,
1996[ISI][Medline].
26.
Phillips, MI.
Functions of angiotensin II in the central nervous system.
Annu Rev Physiol
49:
413-435,
1987[ISI][Medline].
27.
Qadri, F,
Culman J,
Veltmar A,
Maas K,
Rascher W,
and
Unger T.
Angiotensin II-induced vasopressin release is mediated through 1-adrenoceptors and angiotensin II AT1 receptors in the supraoptic nucleus.
J Pharmacol Exp Ther
267:
567-574,
1994
28.
Ren, J,
Karpinshki E,
and
Benishin CG.
The actions of prostaglandin E2 on potassium currents in rat tail artery vascular smooth muscle cells: regulation by protein kinase A and protein kinase C.
J Pharmacol Exp Ther
277:
394-402,
1996
29.
Richards, EM,
Raizada MK,
Gelband CH,
and
Sumners C.
Angiotensin II type 1 receptor modulated signaling pathways in neurons.
Mol Neurobiol
19:
25-42,
1999[ISI][Medline].
30.
Sabri, A,
Govindarajan G,
Griffin TM,
Byron KL,
Samarel AM,
and
Lucchesi PA.
Calcium- and protein kinase C-dependent activation of the tyrosine kinase PYK2 by angiotensin II in vascular smooth muscle.
Circ Res
83:
841-851,
1998
31.
Shearman, MS,
Sekiguchi K,
and
Nishizuka Y.
Modulation of ion channel activity: a key function of the protein kinase C enzyme family.
Pharmacol Rev
41:
211-237,
1989[Abstract].
32.
Smith, RJ,
Sam LM,
Justen JM,
Bundy GL,
Bala GA,
and
Bleasdale JE.
Receptor-coupled signal transduction in human polymorphonuclear neutrophils: effects of a novel inhibitor of phospholipase C-dependent processes on cell responsiveness.
J Pharmacol Exp Ther
253:
688-697,
1990
33.
Sumners, C,
and
Gelband CH.
Neuronal ion channel signalling pathways: modulation by angiotensin II.
Cell Signal
10:
303-311,
1998[ISI][Medline].
34.
Sumners, C,
Tang W,
Zelezna B,
and
Raizada MK.
Angiotensin II receptor subtypes are coupled with distinct signal transduction mechanisms in neurons and astroglia from rat brain.
Proc Natl Acad Sci USA
88:
7567-7571,
1991
35.
Sumners, C,
Zhu M,
Gelband CH,
and
Posner P.
Angiotensin II type 1 receptor modulation of neuronal K+ and Ca2+ currents: intracellular mechanisms.
Am J Physiol Cell Physiol
271:
C154-C163,
1996
36.
Tsai, W,
Morielli AD,
Cachero TG,
and
Peralta EG.
Receptor protein tyrosine phosphatase- participates in the M1 muscarinic acetylcholine receptor-dependent regulation of Kv1.2 channel activity.
EMBO J
18:
109-118,
1999[ISI][Medline].
37.
Vogalis, F,
Ward M,
and
Horowitz B.
Suppression of two cloned smooth muscle-derived delayed rectifier potassium channels by cholinergic agonists and phorbol esters.
Mol Pharmacol
48:
1015-1023,
1995[Abstract].
38.
Wang, D,
Sumners C,
Gelband CH,
and
Posner P.
Mechanisms underlying the chronotropic effect of angiotensin II on cultured neurons from rat hypothalamus and brainstem.
J Neurophysiol
78:
1013-1020,
1997
39.
Wang, D,
Sumners C,
Posner P,
and
Gelband CH.
A-type K+ current in neurons cultured from neonatal rat hypothalamus and brainstem: modulation by angiotensin II.
J Neurophysiol
78:
1021-1029,
1997
40.
Yang, CR,
Phillips MI,
and
Renaud LP.
Angiotensin II receptor activation depolarizes rat supraoptic neurons in vitro.
Am J Physiol Regulatory Integrative Comp Physiol
263:
R1333-R1338,
1992
41.
Zhu, M,
Gelband CH,
Moore JM,
Posner P,
and
Sumners C.
Angiotensin II type 2 receptor stimulation of neuronal delayed rectifier potassium current involves phospholipase A2 and arachidonic acid.
J Neurosci
18:
679-686,
1998
42.
Zhu, M,
Neubig RR,
Wade SM,
Posner P,
Gelband CH,
and
Sumners C.
Modulation of K+ and Ca2+ currents in cultured neurons by an angiotensin II type 1A receptor peptide.
Am J Physiol Cell Physiol
273:
C1040-C1048,
1997
This article has been cited by other articles:
|
|
 |
|
  T. Endoh Involvement of Src tyrosine kinase and mitogen-activated protein kinase in the facilitation of calcium channels in rat nucleus of the tractus solitarius by angiotensin II J. Physiol., November 1, 2005; 568(3): 851 - 856. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Pallone, C. Cao, and Z. Zhang Inhibition of K+ conductance in descending vasa recta pericytes by ANG II Am J Physiol Renal Physiol, December 1, 2004; 287(6): F1213 - F1222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shimoni and X.-F. Liu Gender differences in ANG II levels and action on multiple K+ current modulation pathways in diabetic rats Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H311 - H319. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Sun, J. Du, C. Sumners, and M. K. Raizada PI3-Kinase Inhibitors Abolish the Enhanced Chronotropic Effects of Angiotensin II in Spontaneously Hypertensive Rat Brain Neurons J Neurophysiol, November 1, 2003; 90(5): 3155 - 3160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-F. WONG, J. W. POLSON, D. MURPHY, J. F. R. PATON, and S. KASPAROV Genetic and pharmacological dissection of pathways involved in the angiotensin II-mediated depression of baroreflex function FASEB J, October 1, 2002; 16(12): 1595 - 1601. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Sun, C. Sumners, and M. K. Raizada Chronotropic Action of Angiotensin II in Neurons via Protein Kinase C and CaMKII Hypertension, February 1, 2002; 39(2): 562 - 566. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
6 experiments.
