A nitric oxide/cyclic GMP-dependent protein kinase pathway alters transmitter release and inhibition by somatostatin at a site downstream of calcium entry

D. Bruce Gray, Luis Polo-Parada, Guillermo R. Pilar, Peau Eang, Ryan R. Metzger, Eric Klann, Stephen D. Meriney

Research output: Contribution to journalArticle

Abstract

We have examined the somatostatin-mediated modulation of acetylcholine release from intact chick embryo choroid tissue and compared these data with those obtained using acutely dissociated neuronal cell bodies from the chick ciliary ganglion. Acetylcholine release, evoked in a calcium-dependent manner by a high potassium (55 mM KCl) stimulation in both preparations, was inhibited almost completely by 100 nM somatostatin. Measurement of intracellular calcium in these neurons revealed that somatostatin blocked the large calcium transient that was observed in control neurons following KCl exposure. The modulatory effect of somatostatin on transmitter release was significantly attenuated by pretreatment with pharmacologic agents that selectively block cyclic GMP (cGMP)-dependent protein kinase (PKG) or nitric oxide (NO) synthase. It is interesting that this prevention of somatostatin- mediated acetylcholine release inhibition occurred without reversal of the somatostatin-mediated block of the KCl-evoked calcium transient. Furthermore, a NO donor or cGMP analogue could block KCl-evoked acetylcholine release, but only cGMP could reduce the KCl-evoked calcium transient. Although cGMP could reduce the KCl-evoked calcium transient, a cGMP analogue was shown to reduce calcium ionophore-evoked transmitter release. Thus, somatostatin reduces acetylcholine release by modulating calcium influx, but the NO-PKG pathway can inhibit acetylcholine release, and alter somatostatin-mediated inhibition, by affecting transmitter release at some point after calcium entry.

Original languageEnglish (US)
Pages (from-to)1981-1990
Number of pages10
JournalJournal of Neurochemistry
Volume72
Issue number5
DOIs
StatePublished - 1999

Fingerprint

Cyclic GMP-Dependent Protein Kinases
Somatostatin
Transmitters
Nitric Oxide
Acetylcholine
Calcium
Cyclic GMP
Neurons
Parasympathetic Ganglia
Choroid
Nitric Oxide Donors
Calcium Ionophores
Chick Embryo
Nitric Oxide Synthase
Potassium
Cells
Modulation
Tissue

Keywords

  • Acetylcholine
  • Calcium
  • Cyclic GMP-dependent protein kinase
  • Nitric oxide

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

A nitric oxide/cyclic GMP-dependent protein kinase pathway alters transmitter release and inhibition by somatostatin at a site downstream of calcium entry. / Gray, D. Bruce; Polo-Parada, Luis; Pilar, Guillermo R.; Eang, Peau; Metzger, Ryan R.; Klann, Eric; Meriney, Stephen D.

In: Journal of Neurochemistry, Vol. 72, No. 5, 1999, p. 1981-1990.

Research output: Contribution to journalArticle

Gray, D. Bruce ; Polo-Parada, Luis ; Pilar, Guillermo R. ; Eang, Peau ; Metzger, Ryan R. ; Klann, Eric ; Meriney, Stephen D. / A nitric oxide/cyclic GMP-dependent protein kinase pathway alters transmitter release and inhibition by somatostatin at a site downstream of calcium entry. In: Journal of Neurochemistry. 1999 ; Vol. 72, No. 5. pp. 1981-1990.
@article{40ba2f01e65d4280bc9dcfe8070cdd4b,
title = "A nitric oxide/cyclic GMP-dependent protein kinase pathway alters transmitter release and inhibition by somatostatin at a site downstream of calcium entry",
abstract = "We have examined the somatostatin-mediated modulation of acetylcholine release from intact chick embryo choroid tissue and compared these data with those obtained using acutely dissociated neuronal cell bodies from the chick ciliary ganglion. Acetylcholine release, evoked in a calcium-dependent manner by a high potassium (55 mM KCl) stimulation in both preparations, was inhibited almost completely by 100 nM somatostatin. Measurement of intracellular calcium in these neurons revealed that somatostatin blocked the large calcium transient that was observed in control neurons following KCl exposure. The modulatory effect of somatostatin on transmitter release was significantly attenuated by pretreatment with pharmacologic agents that selectively block cyclic GMP (cGMP)-dependent protein kinase (PKG) or nitric oxide (NO) synthase. It is interesting that this prevention of somatostatin- mediated acetylcholine release inhibition occurred without reversal of the somatostatin-mediated block of the KCl-evoked calcium transient. Furthermore, a NO donor or cGMP analogue could block KCl-evoked acetylcholine release, but only cGMP could reduce the KCl-evoked calcium transient. Although cGMP could reduce the KCl-evoked calcium transient, a cGMP analogue was shown to reduce calcium ionophore-evoked transmitter release. Thus, somatostatin reduces acetylcholine release by modulating calcium influx, but the NO-PKG pathway can inhibit acetylcholine release, and alter somatostatin-mediated inhibition, by affecting transmitter release at some point after calcium entry.",
keywords = "Acetylcholine, Calcium, Cyclic GMP-dependent protein kinase, Nitric oxide",
author = "Gray, {D. Bruce} and Luis Polo-Parada and Pilar, {Guillermo R.} and Peau Eang and Metzger, {Ryan R.} and Eric Klann and Meriney, {Stephen D.}",
year = "1999",
doi = "10.1046/j.1471-4159.1999.0721981.x",
language = "English (US)",
volume = "72",
pages = "1981--1990",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - A nitric oxide/cyclic GMP-dependent protein kinase pathway alters transmitter release and inhibition by somatostatin at a site downstream of calcium entry

AU - Gray, D. Bruce

AU - Polo-Parada, Luis

AU - Pilar, Guillermo R.

AU - Eang, Peau

AU - Metzger, Ryan R.

AU - Klann, Eric

AU - Meriney, Stephen D.

PY - 1999

Y1 - 1999

N2 - We have examined the somatostatin-mediated modulation of acetylcholine release from intact chick embryo choroid tissue and compared these data with those obtained using acutely dissociated neuronal cell bodies from the chick ciliary ganglion. Acetylcholine release, evoked in a calcium-dependent manner by a high potassium (55 mM KCl) stimulation in both preparations, was inhibited almost completely by 100 nM somatostatin. Measurement of intracellular calcium in these neurons revealed that somatostatin blocked the large calcium transient that was observed in control neurons following KCl exposure. The modulatory effect of somatostatin on transmitter release was significantly attenuated by pretreatment with pharmacologic agents that selectively block cyclic GMP (cGMP)-dependent protein kinase (PKG) or nitric oxide (NO) synthase. It is interesting that this prevention of somatostatin- mediated acetylcholine release inhibition occurred without reversal of the somatostatin-mediated block of the KCl-evoked calcium transient. Furthermore, a NO donor or cGMP analogue could block KCl-evoked acetylcholine release, but only cGMP could reduce the KCl-evoked calcium transient. Although cGMP could reduce the KCl-evoked calcium transient, a cGMP analogue was shown to reduce calcium ionophore-evoked transmitter release. Thus, somatostatin reduces acetylcholine release by modulating calcium influx, but the NO-PKG pathway can inhibit acetylcholine release, and alter somatostatin-mediated inhibition, by affecting transmitter release at some point after calcium entry.

AB - We have examined the somatostatin-mediated modulation of acetylcholine release from intact chick embryo choroid tissue and compared these data with those obtained using acutely dissociated neuronal cell bodies from the chick ciliary ganglion. Acetylcholine release, evoked in a calcium-dependent manner by a high potassium (55 mM KCl) stimulation in both preparations, was inhibited almost completely by 100 nM somatostatin. Measurement of intracellular calcium in these neurons revealed that somatostatin blocked the large calcium transient that was observed in control neurons following KCl exposure. The modulatory effect of somatostatin on transmitter release was significantly attenuated by pretreatment with pharmacologic agents that selectively block cyclic GMP (cGMP)-dependent protein kinase (PKG) or nitric oxide (NO) synthase. It is interesting that this prevention of somatostatin- mediated acetylcholine release inhibition occurred without reversal of the somatostatin-mediated block of the KCl-evoked calcium transient. Furthermore, a NO donor or cGMP analogue could block KCl-evoked acetylcholine release, but only cGMP could reduce the KCl-evoked calcium transient. Although cGMP could reduce the KCl-evoked calcium transient, a cGMP analogue was shown to reduce calcium ionophore-evoked transmitter release. Thus, somatostatin reduces acetylcholine release by modulating calcium influx, but the NO-PKG pathway can inhibit acetylcholine release, and alter somatostatin-mediated inhibition, by affecting transmitter release at some point after calcium entry.

KW - Acetylcholine

KW - Calcium

KW - Cyclic GMP-dependent protein kinase

KW - Nitric oxide

UR - http://www.scopus.com/inward/record.url?scp=0033010061&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033010061&partnerID=8YFLogxK

U2 - 10.1046/j.1471-4159.1999.0721981.x

DO - 10.1046/j.1471-4159.1999.0721981.x

M3 - Article

C2 - 10217275

AN - SCOPUS:0033010061

VL - 72

SP - 1981

EP - 1990

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 5

ER -