RT info:eu-repo/semantics/article
T1 The role of dihydropydine-sensitive Ca2 + channels in stimulus-evoked catecholamine release from chemoreceptor cells of the carotid body
A1 Obeso Cáceres, Ana María de la Luz
A1 Rocher Martín, María Asunción
A1 Sidone, S.
A1 González, Constancio
K1 Cardiovascular, Aparato - Tratamiento
AB Ahatraet-The present study utilized an in vitro preparation of the rabbit carotid body, with tissuecatecholamine stores labeled by incubation with ‘H-tyrosine. The goal was to characterize pharmacologicallythe vol~g~~n&nt Ca*+ channels present in the type I (glomus) cells of this arterial chemoreceptororgan, and to elucidate their role as pathways for Ca2+ entry. We found that release of ‘H-dopamineinduced by high external potassium was over 95% dependent on external cakium concentration and thatthis release was 9&100% inhibited by the dihydropy~~ne antagonists, nisoldipine and nitrendipine, andwas potentiated by the dihydropyridine agonist, BayK 8444. Therefore, any stimulus-induced, cakiumdependentrelease of 3H-dopamine that was inhibited by nisoldipine and potentiated by BayK 8644, wasconsidered to be supported by Ca2+ entry into the cells via voltage-dependent Ca2+ channels. Significantdifferences were observed in the release of ‘H-dopamine induced by 75 vs 25mM K+. On prolongedstimulation, 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 approximately90% by 1.5 mM Co2+ or 625 nM nisoldipine, while release by 25 mM K+ was completely blocked by0.6 mM Co*+ or 125 nM nisoldipine. Low PO,-induced release of 3H-dopamine was 95% dependent onCa*+, and was inhibited by nisoldipine (625 nM) in a manner inversely proportional to the intensity ofhypoxic stimulation, i.e. 79% inhibition at a PO, of 49 Torr, and 20% inhibition at PO2 of 0 Torr. BayK8644 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 shouldoccur mainly through these channels while the release induced by strong hypoxic stimuli will be SetNedby Ca2+ entry which occurs in part via voltage-dependent Ca2+ channels, and in part through anadditional pathway, probably a Na+/Ca2+ exchanger. The insensitivity to dihydropyridines of the releaseof )H-dopamine induced by high 1DC02/low pH, Na+-propionate and dinitrophenol may indicate acomplete 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 becomposite receptors in which the type I (glomus) cellsdetect changes in blood PO,, PCO, and pH andrespond with the release of neurotransmitt~ toactivate the closely apposed chemosensory nerveterminals.~** One such neurotransmitter that hasreceived considerable attention in recent yearsand is known to be released by the type I cells isdopamine (DA). This biogenic amine has beenshown to be released in proportion to both theintensity of stimulation and the resultant sensorydischarge 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
PB Pergamon Press
SN 0306-4522
YR 1992
FD 1992
LK http://uvadoc.uva.es/handle/10324/6619
UL http://uvadoc.uva.es/handle/10324/6619
LA eng
NO Neuroscience, vol.47, n.2. p.463-472
NO Producción Científica
DS UVaDOC
RD 19-nov-2024