Por favor, use este identificador para citar o enlazar este ítem:http://uvadoc.uva.es/handle/10324/6619
Título
The role of dihydropydine-sensitive Ca2 + channels in stimulus-evoked catecholamine release from chemoreceptor cells of the carotid body
Autor
Año del Documento
1992
Editorial
Pergamon Press
Descripción
Producción Científica
Documento Fuente
Neuroscience, vol.47, n.2. p.463-472
Resumo
Ahatraet-The present study utilized an in vitro preparation of the rabbit carotid body, with tissue
catecholamine stores labeled by incubation with ‘H-tyrosine. The goal was to characterize pharmacologically
the vol~g~~n&nt Ca*+ channels present in the type I (glomus) cells of this arterial chemoreceptor
organ, and to elucidate their role as pathways for Ca2+ entry. We found that release of ‘H-dopamine
induced by high external potassium was over 95% dependent on external cakium concentration and that
this release was 9&100% inhibited by the dihydropy~~ne antagonists, nisoldipine and nitrendipine, and
was potentiated by the dihydropyridine agonist, BayK 8444. Therefore, any stimulus-induced, cakiumdependent
release of 3H-dopamine that was inhibited by nisoldipine and potentiated by BayK 8644, was
considered to be supported by Ca2+ entry into the cells via voltage-dependent Ca2+ channels. Significant
differences were observed in the release of ‘H-dopamine induced by 75 vs 25mM K+. On prolonged
stimulation, release induced by 75 mM K+ was large and transient, whilst that induced by 25 mM K+,
although more moderate, was sustained. The release elicited by 75 mM K+ was inhibited approximately
90% by 1.5 mM Co2+ or 625 nM nisoldipine, while release by 25 mM K+ was completely blocked by
0.6 mM Co*+ or 125 nM nisoldipine. Low PO,-induced release of 3H-dopamine was 95% dependent on
Ca*+, and was inhibited by nisoldipine (625 nM) in a manner inversely proportional to the intensity of
hypoxic stimulation, i.e. 79% inhibition at a PO, of 49 Torr, and 20% inhibition at PO2 of 0 Torr. BayK
8644 potentiatcd the release induced by moderate hypoxic stimuli. Release elicited by high PCOJlow pH,
or by Na+-propionate or dinitrophenol~n~ining solutions, was approximately 80% Ca’+-dependent,
and the ~hyd~y~din~ failed to modify this release.
It is concluded that type I mlls possess vol~~de~nd~t Ca ‘+ channels sensitive to the dihydropy~dines,
which in agreement with previous el~trophysiolo~~l data should be defined as L-type Ca*+
channels. Calcium entry which supports the release of 3H-dopamine elicited by moderate hypoxia should
occur mainly through these channels while the release induced by strong hypoxic stimuli will be SetNed
by Ca2+ entry which occurs in part via voltage-dependent Ca2+ channels, and in part through an
additional pathway, probably a Na+/Ca2+ exchanger. The insensitivity to dihydropyridines of the release
of )H-dopamine induced by high 1DC02/low pH, Na+-propionate and dinitrophenol may indicate a
complete loss of efficacy of the drugs to modulate Ca 2+ channels under these conditions or more likely,
that other mechanisms are activated, probably the Na+-Ca’+ exchanger.
Carotid body (CB) chemoreceptors are thought to be
composite receptors in which the type I (glomus) cells
detect changes in blood PO,, PCO, and pH and
respond with the release of neurotransmitt~ to
activate the closely apposed chemosensory nerve
terminals.~** One such neurotransmitter that has
received considerable attention in recent years
and is known to be released by the type I cells is
dopamine (DA). This biogenic amine has been
shown to be released in proportion to both the
intensity of stimulation and the resultant sensory
discharge recorded from the carotid sinus nerve
$To whom correspondence should be addressed.
Abbr~~~~~~ CB, carotid body; CSN, carotid sinus nerve;
DA, dopamine; DHMA, dihydrox~~delic acid,
DOPAC, dihydroxyphenyl acetic acid; NE, norepinephrine.
(CSN). This relationship between stimulus
Materias (normalizadas)
Cardiovascular, Aparato - Tratamiento
ISSN
0306-4522
Revisión por pares
Sí
Idioma
eng
Derechos
openAccess
Aparece en las colecciones
Arquivos deste item
![Attribution-NonCommercial-NoDerivatives 4.0 International](/themes/Mirage2//images/creativecommons/cc-by-nc-nd.png)