3H-noradrenaline release from rat neocortical slices in the absence of extracellular Ca2+ and its presynaptic alpha 2-adrenergic modulation. A study on the possible role of cyclic AMP.

Naunyn-Schmiedeberg's archives of pharmacology ·Vol. 323 ·No. 3 ·1983-07-00 ·Pages 188-92

Schoffelmeer AN, Mulder AH

Abstract

In Ca2+ -free EGTA-containing medium veratrine (3-25 microM) concentration-dependently enhanced the efflux of 3H-noradrenaline from (radiolabelled) rat neocortical slices. Clonidine (1 microM) inhibited and phentolamine (3 microM) enhanced veratrine-induced 3'-noradrenaline release and the modulatory effects were inversely related to the veratrine concentration used. Dibutyryl-cyclic AMP, 8-Bromo-cyclic AMP (10 microM--3 mM) and the adenylate cyclase activators NaF (2 mM) and forskolin (10 microM) enhanced 3H-noradrenaline release induced by 3 microM veratrine, but had no effect on spontaneous tritium efflux. In the presence of these drugs the modulatory effects of clonidine and phentolamine on 3H-noradrenaline release were reduced as expected from the enhanced efficacy of veratrine. In contrast to these drugs the selective cyclic AMP-phosphodiesterase inhibitor ZK 62771 reduced veratrine (3 microM)-induced 3H-noradrenaline release in Ca2+ -free medium. In the presence of 1.2 mM Ca2+, 3H-noradrenaline release induced by 13 mM K+ was also inhibited. However, when 3H-noradrenaline release was effected in the presence of tetrodotoxin (0.3 microM) or by electrical field-stimulation (1 Hz), ZK 62771 slightly but significantly enhanced the release. It is postulated that cyclic AMP is involved in the secretion process in central noradrenergic varicosities and that presynaptic alpha2-adrenoceptors upon activation inhibit the secretion process through an inhibition of a presynaptically located adenylate cyclase.

MeSH Terms

Animals Bucladesine/pharmacology Calcium/physiology Cerebral Cortex/drug effects,metabolism Colforsin Cyclic AMP/physiology Diterpenes/pharmacology In Vitro Techniques Male Norepinephrine/metabolism Rats Rats, Inbred Strains Receptors, Adrenergic, alpha/physiology Sodium Fluoride/pharmacology Veratrine/pharmacology

Chemicals

Diterpenes Receptors, Adrenergic, alpha Colforsin Bucladesine Sodium Fluoride Cyclic AMP Veratrine Calcium Norepinephrine

Authors & Affiliations

2 authors, click to expand affiliations / ORCID

Schoffelmeer A N

Mulder A H

References (29)

29 references, click to expand

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Article Info

Journal

Naunyn-Schmiedeberg's archives of pharmacology

Abbr.

Naunyn Schmiedebergs Arch Pharmacol

ISSN

0028-1298

DOI

10.1007/BF00497661

Published

1983-07-00

Pages

188-92

Language

English

Region

Germany

NLM ID

0326264

Subset

External Links

PubMed source DOI: 10.1007/BF00497661 View journal details

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3H-noradrenaline release from rat neocortical slices in the absence of extracellular Ca2+ and its presynaptic alpha 2-adrenergic modulation. A study on the possible role of cyclic AMP.

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