Receptor-induced Ca(2+) signaling in cultured myenteric neurons.
We studied the effect of excitatory neurotransmitters (10(-5) M) on the intracellular Ca(2+) concentration ([Ca(2+)](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 [Ca(2+)](i) rise in 68.2% of the neurons, which was highly dependent on Ca(2+) release from intracellular stores, since after thapsigargin (5 microM) pretreatment only 8% responded. The responses to serotonin, present in 90.7%, were completely blocked by ondansetron (10(-5) M), a 5-HT(3) receptor antagonist. Specific agonists of other serotonin receptors were not able to induce a [Ca(2+)](i) rise. Removing extracellular Ca(2+) 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 Ca(2+) stores, and the 5-HT(3) receptor mediates the serotonin-induced Ca(2+) signaling in cultured myenteric neurons.
vanden Berghe
P
P
Center for Gastroenterological Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
Tack
J
J
Andrioli
A
A
Missiaen
L
L
Janssens
J
J
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D006168:Guinea Pigs; D007425:Intracellular Membranes / Q000378:metabolism; D009197:Myenteric Plexus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000502:physiology; D009994:Osmolar Concentration; D011956:Receptors, Cell Surface / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology
D018377:Neurotransmitter Agents; D011956:Receptors, Cell Surface; D012701:Serotonin; D013373:Substance P; D000109:Acetylcholine; D002118:Calcium