Protein kinase C activators mimic the M2-muscarinic receptor-mediated effects on the action potential in isolated sympathetic neurons of rabbits

doi:10.1016/0304-3940(88)90571-X

Neuroscience Letters

Volume 86, Issue 2, 31 March 1988, Pages 201-206

https://doi.org/10.1016/0304-3940(88)90571-X Get rights and content

Abstract

Protein kinase C activators 1,2-oleoylacetylglycerol (OAG, 0.5–50 μM), a synthetic diacylglycerol analog, and phorbol-12,13-dibutyrate (Pb(Bu)₂, 0.016–1.6 μM) depressed the calcium (Ca)-dependent components of action potentials in isolated superior cervical ganglion cells of rabbits. Similar depressions were elicited when the M₂-muscarinic receptors were activated. This muscarinic modification of the action potential was obscured after the perfusion with protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7, 50 μM). It seems that protein kinase C is an intermediator between the M₂-muscarinic receptors and the Ca channels regulating the firing rate of the postganglionic cells.

References (15)

M. Castagna et al.
Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters
J. Biol. Chem.
(1982)
D.A. Greenberg et al.
Interaction of calmodulin inhibitors and protein kinase C inhibitors with voltage-dependent calcium channels
Brain Res.
(1987)
K. Kaibuchi et al.
Synergistic functions of protein phosphorylation and calcium mobilization in platelet activation
J. Biol. Chem.
(1983)
J.F. Kuo et al.
Cobra polypeptide cytotoxin I and marine worm polypeptide cytotoxin A-IV are potent and selective inhibitors of phospholipid-sensitive Ca²⁺-dependent protein kinase
FEBS Lett.
(1983)
S. Mochida et al.
Multiple muscarinic responses directly evoked in isolated neurones dissociated from rabbit sympathetic ganglia
J. Autonom. Nerv. Syst.
(1986)
S. Mochida et al.
Activation of M₂ muscarinic receptors causes an alteration of action potentials by modulation of Ca entry in isolated sympathetic neurons of rabbits
Neurosci. Lett.
(1986)
M.R. Pickard et al.
Effects of surugatoxin and other nicotinic and muscarinic antagonists on phosphatidyl inositol metabolism in active sympathetic ganglia
Biochem. Pharmacol.
(1977)

There are more references available in the full text version of this article.

Cited by (10)

Coupling of M<inf>2</inf> muscarinic receptors to membrane ion channels via phosphoinositide 3-kinase γ and atypical protein kinase C
1999, Journal of Biological Chemistry
We report a novel signaling pathway linking M₂ muscarinic receptors to metabotropic ion channels. Stimulation of heterologously expressed M₂ receptors, but not other G_i/G_o-associated receptors (M₄ or α_2c), activates a calcium- and voltage-independent chloride current in Xenopus oocytes. We show that the stimulatory pathway linking M₂ receptors to these chloride channels consists of Gβγ stimulation of phosphoinositide 3-kinase γ (PI-3Kγ), formation of phosphatidylinositol 3,4,5-trisphosphate (PIP₃), and activation of atypical protein kinase C (PKC). The chloride current is activated in the absence of M₂ receptor stimulation by the injection of PIP₃, and PIP₃ current activation is blocked by a pseudosubstrate inhibitory peptide of atypical PKC but not other PKCs. Moreover, the current is activated by injection of recombinant PKCζ at concentrations as low as 1 nm. M₂ receptor-current coupling was disrupted by inhibiton of PI-3K and by injection of βγ binding peptides, but it was not affected by expression of dominant negative p85 cRNA. We also show that this pathway mediates M₂ receptor coupling to metabotropic nonselective cation channels in mammalian smooth muscle cells, thus demonstrating the broad relevance of this signaling cascade in neurotransmitter signaling.
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Norepinephrine (NE) and γ-aminobutyric acid (GABA) inhibit N -type calcium channels in embryonic chick sensory neurons. We demonstrate here that the modulatory actions of the two transmitters are mediated through distinct biochemical pathways. Intracellular application of the pseudosubstrate inhibitor for protein kinase C blocks the inhibition produced by NE (and the protein kinase C activator oleoylacetylglycerol), but not that produced by GABA. Calcium current inhibition produced by oleoylacetylglycerol occludes inhibition by subsequent application of NE; GABA-mediated inhibition, however, is not eliminated by prior activation of protein kinase C. These results demonstrate that multiple biochemical pathways converge to control N-type calcium channel function.
Different GTP-binding proteins mediate regulation of calcium channels by acetylcholine and noradrenaline in rat sympathetic neurons
1989, Brain Research
In dissociated neurons of rat superior cervical ganglion (SCG), noradrenaline (NA) and acetylcholine (ACh) suppressed Ca²⁺ currents elicited by depolarizations to 0 mV from t-60 mV. With GTP-γ-S in patch electrodes, ACh and NA caused persistent inhibition of Ca²⁺ currents. Pretreatment of SCG cells with pertussis toxin abolished the action of ACh but not of NA. The results suggest that ACh and NA reduce the Ca²⁺ currents in SCG cells through different G proteins.
GTP-binding proteins mediate the M<inf>2</inf>-muscarinic effect on the action potential in isolated sympathetic neurons of rabbits
1988, Neuroscience Letters
Activation of M₂-muscarinic receptors alters the configuration of the action potential due to depression of the calcium-dependent components, the shoulder in the falling phase and the afterhyperpolarization, in isolated superior cervical ganglionic neurons of rabbits. This effect was inhibited by preincubation of the cells with pertussis toxin, or by the intracellular administration of guanosine 5′-O-(2-thiodiphosphate) (GDP-β-S). The muscarinic effect persisted in the cells loaded with guanosine 5′-O-(3-thiotriphosphate) (GTP-γ-S). Intracellular application of cAMP and 3-isobutyl-1-methylxanthine did not change the muscarinic effect. The results suggest that a GTP-binding protein is involved in the cAMP-independent, M₂-muscarinic receptor-mediated regulation of action potential firing in sympathetic neurons.
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1997, Journal of Neurophysiology
Involvement of a phorbol ester-insensitive protein kinase C in the α<inf>2</inf>- adrenergic inhibition of voltage-gated calcium current in chick sympathetic neurons
1996, Journal of Neuroscience

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Protein kinase C activators mimic the M2-muscarinic receptor-mediated effects on the action potential in isolated sympathetic neurons of rabbits

Abstract

J. Biol. Chem.

Brain Res.

J. Biol. Chem.

FEBS Lett.

J. Autonom. Nerv. Syst.

Neurosci. Lett.

Biochem. Pharmacol.

Protein kinase C activators mimic the M₂-muscarinic receptor-mediated effects on the action potential in isolated sympathetic neurons of rabbits