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1 Center for Gastroenterological Research and 2 Department of Physiology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium
We studied the effect of excitatory
neurotransmitters (10
5 M) on the
intracellular Ca2+ concentration
([Ca2+]i) of cultured myenteric
neurons. ACh evoked a response in 48.6% of the neurons. This response
consisted of a fast and a slow component, respectively mediated by
nicotinic and muscarinic receptors, as revealed by specific agonists
and antagonists. Substance P evoked a
[Ca2+]i rise in 68.2% of the
neurons, which was highly dependent on Ca2+ release from
intracellular stores, since after thapsigargin (5 µM) pretreatment
only 8% responded. The responses to serotonin, present in 90.7%, were
completely blocked by ondansetron (105
M), a 5-HT3 receptor antagonist. Specific agonists of other
serotonin receptors were not able to induce a
[Ca2+]i rise. Removing
extracellular Ca2+ abolished all serotonin and fast ACh
responses, whereas substance P and slow ACh responses were more
persistent. We conclude that ACh-induced signaling involves both
nicotinic and muscarinic receptors responsible for a fast and a more
delayed component, respectively. Substance P-induced signaling requires
functional intracellular Ca2+ stores, and the
5-HT3 receptor mediates the serotonin-induced Ca2+ signaling in cultured myenteric neurons.
enteric nervous system; calcium channel; enteric neuron
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