Receptor-induced Ca2+ signaling in cultured myenteric neurons

We studied the effect of excitatory neurotransmitters (10(-5) M) on the int racellular Ca2+ concentration ([Ca2+](i)) of cultured myenteric neurons. AC h evoked a response in 48.6% of the neurons. This response consisted of a f ast and a slow component, respectively mediated by nicotinic and muscarinic receptors, as revealed by specific agonists and antagonists. Substance P e voked a [Ca2+](i) rise in 68.2% of the neurons, which was highly dependent on Ca2+ release from intracellular stores, since after thapsigargin (5 mu M ) pretreatment only 8% responded. The responses to serotonin, present in 90 .7%, were completely blocked by ondansetron (10(-5) M), a 5-HT3 receptor an tagonist. Specific agonists of other serotonin receptors were not able to i nduce a [Ca2+](i) rise. Removing extracellular Ca2+ abolished all serotonin and fast ACh responses, whereas substance P and slow ACh responses were mo re persistent. We conclude that ACh-induced signaling involves both nicotin ic and muscarinic receptors responsible for a fast and a more delayed compo nent, respectively. Substance P-induced signaling requires functional intra cellular Ca2+ stores, and the 5-HT3 receptor mediates the serotonin-induced Ca2+ signaling in cultured myenteric neurons.