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 journalArticlepeer-review

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

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'A nitric oxide/cyclic GMP-dependent protein kinase pathway alters transmitter release and inhibition by somatostatin at a site downstream of calcium entry'. Together they form a unique fingerprint.

Cite this