 |
 Previous Article | Next Article 
Journal of Neuroscience, Vol 15, 4580-4591, Copyright © 1995 by Society for Neuroscience
Differential regulation of sympathetic neuron neuropeptide Y and catecholamine content and secretion
V May, CA Brandenburg and KM Braas
Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington 05405, USA.
Cultured principal neurons of the superior cervical ganglion (SCG), which
coexpress high levels of catecholamines and neuropeptide Y (NPY), were used
as a model to simultaneously examine whether sympathetic neuronal peptide
and transmitter content or secretion are differentially regulated.
Accumulation of NPY immunoreactivity and the dopamine metabolites DOPAC and
HVA in SCG neuronal conditioned culture medium was used as an index of NPY
and catecholamine secretion, respectively. Release of NPY and
catecholamines was linear with time; SCG neurons exhibited a basal NPY
secretory rate of approximately 0.9-3 fmol NPY immunoreactivity/10(4)
cells/hr, and basal DOPAC plus HVA accumulation was about 10-20 pmol total
metabolites/10(4) cells/hr. While sympathetic neuronal NPY and total
catecholamine cell content increased more than 6-10-fold by 14 d of
culture, secretion remained constant. Depolarization stimulated the rate of
NPY secretion 18-fold, whereas medium catecholamine metabolite levels
increased 3-fold. Activation of intracellular signaling pathways was shown
to be an important point of regulation of sympathetic neuron peptide and
transmitter content and secretion. Differential regulation of SCG neuron
NPY and catecholamine expression was second messenger system specific.
Activation of the protein kinase A pathway with the cAMP analog dibutyryl
cAMP, or the adenylyl cyclase activator forskolin, produced a
concentration-dependent, sustained stimulation of NPY secretion; maximal
stimulation resulted in decreased cellular NPY content. Parallel stimulated
neuronal catecholamine release was observed, but in contrast to NPY, total
cellular catecholamine content was also increased. Regulation of the
protein kinase C pathway with phorbol myristate acetate (PMA) stimulated
SCG neuronal NPY secretion to a lesser degree than activation of protein
kinase A, but did not alter cellular NPY levels. PMA minimally stimulated
catecholamine release and content. NPY secretion induced by the calcium
ionophore A23187 was paralleled by a concomitant decrease in cellular NPY.
A23187 decreased catecholamine release, but did not change cellular total
catecholamine levels. The magnitude of the secretory responses of
sympathetic neurons to these regulators was far greater than changes in NPY
or catecholamine content, biosynthesis or mRNA levels, suggesting that
release is a primary site of regulation. The independent regulation of
sympathetic neuronal NPY and catecholamine content and release is
consistent with the fundamental differences in the biosynthetic pathways,
vesicular compartmentalization, uptake and metabolism of neuropeptides and
neurotransmitters.
This article has been cited by other articles:
|
|
|
|
 
D. H. Damon
TH and NPY in sympathetic neurovascular cultures: role of LIF and NT-3
Am J Physiol Cell Physiol,
January 1, 2008;
294(1):
C306 - C312.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. H. Damon
Sympathetic innervation promotes vascular smooth muscle differentiation
Am J Physiol Heart Circ Physiol,
June 1, 2005;
288(6):
H2785 - H2791.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Seyedi, C. J. Mackins, T. Machida, A. C. Reid, R. B. Silver, and R. Levi
Histamine H3-Receptor-Induced Attenuation of Norepinephrine Exocytosis: A Decreased Protein Kinase A Activity Mediates a Reduction in Intracellular Calcium
J. Pharmacol. Exp. Ther.,
January 1, 2005;
312(1):
272 - 280.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Simonneaux and C. Ribelayga
Generation of the Melatonin Endocrine Message in Mammals: A Review of the Complex Regulation of Melatonin Synthesis by Norepinephrine, Peptides, and Other Pineal Transmitters
Pharmacol. Rev.,
June 1, 2003;
55(2):
325 - 395.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. May, M. R. Schiller, B. A. Eipper, and R. E. Mains
Kalirin Dbl-Homology Guanine Nucleotide Exchange Factor 1 Domain Initiates New Axon Outgrowths via RhoG-Mediated Mechanisms
J. Neurosci.,
August 15, 2002;
22(16):
6980 - 6990.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Beaudet, R. L. Parsons, K. M. Braas, and V. May
Mechanisms Mediating Pituitary Adenylate Cyclase-Activating Polypeptide Depolarization of Rat Sympathetic Neurons
J. Neurosci.,
October 1, 2000;
20(19):
7353 - 7361.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Marx, R. El Meskini, D. C. Johns, and R. E. Mains
Differences in the Ways Sympathetic Neurons and Endocrine Cells Process, Store, and Secrete Exogenous Neuropeptides and Peptide-Processing Enzymes
J. Neurosci.,
October 1, 1999;
19(19):
8300 - 8311.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. M. Braas and V. May
Pituitary Adenylate Cyclase-activating Polypeptides Directly Stimulate Sympathetic Neuron Neuropeptide Y Release through PAC1 Receptor Isoform Activation of Specific Intracellular Signaling Pathways
J. Biol. Chem.,
September 24, 1999;
274(39):
27702 - 27710.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. M. Braas, V. May, S. A. Harakall, J. C. Hardwick, and R. L. Parsons
Pituitary Adenylate Cyclase-Activating Polypeptide Expression and Modulation of Neuronal Excitability in Guinea Pig Cardiac Ganglia
J. Neurosci.,
December 1, 1998;
18(23):
9766 - 9779.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. A. Brandenburg, V. May, and K. M. Braas
Identification of Endogenous Sympathetic Neuron Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP): Depolarization Regulates Production and Secretion through Induction of Multiple Propeptide Transcripts
J. Neurosci.,
June 1, 1997;
17(11):
4045 - 4055.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
