Presynaptic autoinhibition of central noradrenaline release in vitro: operational characteristics and effects of drugs acting at alpha-2 adrenoceptors in the presence of uptake inhibition

Journal Article · Wed Jun 01 04:00:00 EDT 1988 · J. Pharmacol. Exp. Ther.; (United States)

OSTI ID:6908829

Valenta, B; Drobny, H; Singer, E A

Functional characteristics of autoinhibition of central noradrenaline release were studied in the presence of uptake inhibition. Slices of rat cerebral cortex were incubated with (3H)noradrenaline, superfused and field-stimulated with 1 to 16 monophasic rectangular pulses at frequencies of 0.02 to 40 Hz. 1) Substances acting at presynaptic alpha-2 adrenoceptors were identified as antagonists, agonists or partial agonists by comparing their effects on 3H-overflow evoked by a single pulse or by two consecutive pulses at 1 Hz. 2) When 1 to 16 pulses were delivered at 0.02, 0.08, 0.3 and 1 Hz to stimulate outflow of tritium, a frequency-dependent suppression of responses to the second and the following pulses was observed. In the presence of the alpha-2 adrenoceptor antagonist idazoxan (10(-6) M), comparable amounts of tritium were released by the first stimulus and each of the following stimuli at 0.02 Hz. In contrast, at 0.08, 0.3 and 1 Hz the amount of 3H-overflow evoked by the first pulse was not reached in response to the following pulses. Clonidine (10(-6) M) diminished markedly the response to the first as well as to the following stimuli, irrespective of the frequency of stimulation. 3) Using two consecutive pulses delivered with decreasing pulse intervals, an apparent reduction or complete abolition of autoinhibition was observed at intervals of less than 100 msec, indicated by reduction or loss of the facilitatory effects of alpha-2 adrenoceptor antagonists. The present results provide detailed insights in operational characteristics of alpha-2 adrenoceptor-mediated autoinhibition and the effects of drugs on this regulatory mechism.

• Research Organization: Univ. of Vienna (Austria)
• OSTI ID: 6908829
• Journal Information: J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 245:3; ISSN JPETA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
DRUGS
IN VITRO
INHIBITION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NEUROREGULATORS
NORADRENALINE
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SECRETION
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
UPTAKE
VERTEBRATES