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Agonist‐mediated regulation of presynaptic receptor function during development of rat septal neurons in culture
Author(s) -
Ehret Andreas,
Birthelmer Anja,
Rutz Susanne,
Riegert Céline,
Rothmaier Anna Katharina,
Jackisch Rolf
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04598.x
Subject(s) - autoreceptor , oxotremorine , muscarinic acetylcholine receptor , acetylcholine , medicine , endocrinology , inhibitory postsynaptic potential , carbachol , biology , agonist , chemistry , stimulation , receptor , biochemistry
Presynaptic receptors modulating the release of acetylcholine (ACh) were studied in fetal septal neurons cultured in a growth medium to which various drugs were added from day 3 in vitro (DIV 3) to DIV 14. The influence of these drugs on the function of the presynaptic muscarinic (M‐) autoreceptor was determined at DIV 14 by measuring the inhibitory effect of the M‐agonist oxotremorine on the electrically‐evoked release of [³H]ACh from cultures pre‐incubated with [³H]choline. The presence of the M‐agonists oxotremorine (100 μmol/L) or carbachol (100 μmol/L) from DIV 3 to DIV 14, or from DIV 13 to DIV 14, abolished M‐autoreceptor function at DIV 14, whereas the presence of the M‐antagonist atropine (10 μmol/L from DIV 3 to DIV 14) during growth left M‐autoreceptor function unaltered. Inhibition of ACh esterase by donepezil (1 μmol/L from DIV 3 to DIV 14) weakly decreased M‐autoreceptor function at DIV 14; inhibition of neuronal firing by 0.1 tetrodotoxin (0.1 μmol/L from DIV 3 to DIV 14) did not tend to affect M‐autoreceptor function at DIV 14. Co‐cultivation of fetal septal and raphe neurons for 2 weeks yielded cell cultures containing both vesicular ACh transporter‐ and tryptophan hydroxylase‐immunopositive cells. From these cultures, the release of both [³H]ACh and [³H]5‐HT could be induced by electrical field stimulation. In co‐cultured neurons versus septal‐only ones the inhibitory effect of oxotremorine on the evoked release of [³H]ACh appeared almost normal, whereas that of the selective 5‐HT 1B agonist 3‐(1,2,5,6‐tetrahydropyrid‐4‐yl)pyrrollo[3,2‐b]pyrid‐5‐one (CP‐93,129) was completely abolished. The effects of CP‐93,129 were also absent on DIV 14 in septal mono‐cultures grown in the presence of CP‐93,129 (10 μmol/L) from DIV 3 to DIV 14. It is therefore concluded that the regulation of presynaptic receptor function strongly depends on the concentrations of endogenous transmitters in the neuronal environment.