Evidence for a presynaptic adenylate cyclase system facilitating (TH)norepinephrine release from rat brain neocortex slices and synaptosomes

Journal Article · Tue Oct 01 04:00:00 EDT 1985 · J. Neurosci.; (United States)

OSTI ID:6182017

Schoffelmeer, A N; Hogenboom, F; Mulder, A H

The effects of drugs known to enhance intracellular cyclic AMP levels on depolarization-induced (TH)norepinephrine release from superfused rat neocortical slices and synaptosomes were investigated. The adenylate cyclase activator forskolin, the membrane-permeating cyclic AMP analogues 8-bromo-cyclic AMP and dibutyryl cyclic AMP, as well as the phosphodiesterase inhibitors isobutylmethylxanthine and 4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrolidone (ZK 62771) enhanced the electrically evoked release of (TH)norepinephrine from superfused rat brain neocortex slices. 8-Bromo-cyclic GMP was without effect on the electrically evoked release. When (TH)norepinephrine release was enhanced by prolonging the electrical pulse duration from 2 msec to 10 msec, the relative inhibitory effect of the CaS channel blocker CdS and the relative facilitatory effect of the K+ channel blocker 4-aminopyridine remained unaffected. In striking contrast, the relative facilitatory effects of forskolin and 8-bromo-cyclic AMP were strongly reduced, whereas the effect of ZK 62771 was almost doubled. When veratrine-induced release of (TH)norepinephrine from cortex synaptosomes was examined, the facilitatory effects of forskolin, 8-bromo-cyclic AMP, and ZK 62771 were even more pronounced than in brain slices. The data strongly support the hypothesis that a presynaptic adenylate cyclase system plays a facilitatory role in the stimulus-secretion coupling process in central noradrenergic nerve terminals.

• Research Organization: Free Univ. Medical Faculty, Amsterdam, Netherland
• OSTI ID: 6182017
• Journal Information: J. Neurosci.; (United States), Journal Name: J. Neurosci.; (United States) Vol. 10; ISSN JNRSD
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
AMP
ANIMAL CELLS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMISTRY
BIOSYNTHESIS
BODY
BRAIN
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CEREBRAL CORTEX
CEREBRUM
CHEMICAL ACTIVATION
CHEMISTRY
DRUGS
ELECTRIC CONDUCTIVITY
ELECTRICAL PROPERTIES
ENZYME INHIBITORS
ENZYMES
HORMONES
LABELLED COMPOUNDS
MAMMALS
MEMBRANES
NERVE CELLS
NERVOUS SYSTEM
NEUROREGULATORS
NORADRENALINE
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PHYSICAL PROPERTIES
RATS
RODENTS
SOMATIC CELLS
STEROID HORMONES
SYMPATHOMIMETICS
SYNTHESIS
TRANSFERASES
TRITIUM COMPOUNDS
VERTEBRATES