ON THE MECHANISM OF PRE-SYNAPTIC AUTORECEPTOR-MEDIATED INHIBITION OF TRANSMITTER SYNTHESIS IN DOPAMINERGIC NERVE-TERMINALS

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dc.contributor.authorBITRAN, M
dc.contributor.authorBUSTOS, G
dc.date.accessioned2025-01-23T19:44:03Z
dc.date.available2025-01-23T19:44:03Z
dc.date.issued1982
dc.description.abstractThe effect of apomorphine (APO) upon dopamine (DA) synthesis and release from rat striatal slices was studied. The synthesis of DA was measured by incubating the slices in Krebs-Ringer phosphate (KRP) medium of variable ionic compositon containing L-tyrosine[14C-U] as DA precursor. A superfusion system was used to study both spontaneous and K+-induced release of labeled DA from striatal slices. The addition of APO directly to the normal KRP medium markedly blocked the formation of [14C]DA from [14C]Tyr with an IC50 [median inhibitory concentration] of 1.8 .times. 10-7 M. Haloperidol (4 .times. 10-7 M), a known DA antagonist, produced a shift to the right of the concentration-response curve for APO inhibition on DA synthesis, whereas the DA antagonist (+)butaclamol (4 .times. 10-7 M) completely reversed the inhibition caused by APO (2 .times. 10-7 M). DA uptake blockers, such as benztropine (2 .times. 10-6 M) or cocaine (1 .times. 10-5 M), did not affect the ability of APO to inhibit DA synthesis. The .alpha.2-adrenergic agonist clonidine produced only a mild inhibition and the .beta.-adrenergic agonist isoproterenol produced no inhibition of [14C]DA formation. APO was able to inhibit DA formation in the absence of Ca in the incubation medium or in the presence of high external Ca concentrations (4, 8 and 24 mM) which depress the rate of DA synthesis. Incubation conditions that cause an increase of free intraneuronal Ca concentrations, such as Na+-free medium, the presence of ouabain (1 .times. 10-4 M), or K+ depolarization, dramatically abolished or impaired the ability of APO to inhibit DA synthesis in striatal slices. It was not possible to demonstrate any change in spontaneous and K+ (27 mM)-induced release of DA in the presence of APO concentrations that produced a marked inhibition of DA synthesis. Tissue slices can evidently be used as a valuable experimental tool to study the inhibitory effect of APO on DA synthesis; this effect occurs through an interaction of APO with presynaptic DA autoreceptors located in striatal dopaminergic nerve terminals. The results do not correlate with the autoreceptor-mediated inhibition of DA synthesis occurring through regulation of Ca influx into the DA nerve terminals. A sensitivity to high intraneuronal Ca concentration may exist during the events that mediate APO-DA autoreceptor interaction and DA synthesis inhibition. DA-synthesis-modulating autoreceptors apparently do not participate in the modulation of DA release.
dc.fuente.origenWOS
dc.identifier.eissn1873-2968
dc.identifier.issn0006-2952
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/99925
dc.identifier.wosidWOS:A1982PH25100002
dc.issue.numero18
dc.language.isoen
dc.pagina.final2860
dc.pagina.inicio2851
dc.revistaBiochemical pharmacology
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleON THE MECHANISM OF PRE-SYNAPTIC AUTORECEPTOR-MEDIATED INHIBITION OF TRANSMITTER SYNTHESIS IN DOPAMINERGIC NERVE-TERMINALS
dc.typeartículo
dc.volumen31
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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