Galanin inhibition of voltage-dependent Ca2+ influx in rat cultured myenteric neurons is mediated by galanin receptor 1

Laura Anselmi, Salvatore L. Stella, Nicholas C. Brecha, Catia Sternini

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Galanin activates three receptors, the galanin receptor 1 (GalR1), GalR2, and GalR3. In the gastrointestinal tract, GalR1 mediates the galanin inhibition of cholinergic transmission to the longitudinal muscle and reduction of peristalsis efficiency in the small intestine. Galanin has also been shown to inhibit depolarizationevoked Ca2+ increases in cultured myenteric neurons. Because GalR1 immunoreactivity is localized to cholinergic myenteric neurons, we hypothesized that this inhibitory action of galanin on myenteric neurons is mediated by GalR1. We investigated the effect of galanin 1-16, which has high affinity for GalR1 and GalR2, in the presence or absence of the selective GalR1 antagonist, RWJ-57408, and of galanin 2-11, which has high affinity for GalR2 and GalR3, on Ca2+ influx through voltage-dependent Ca2+ channels in cultured myenteric neurons. Myenteric neurons were loaded with fluo-4 and depolarized by high K+ concentration to activate voltage-dependent Ca2+ channels. Intracellular Ca2+ levels were quantified with confocal microscopy. Galanin 1-16 (0.01-1 μM) inhibited the depolarization- evoked Ca2+ increase in a dose-dependent manner with an EC50 of 0.172 μM. The selective GalR1 antagonist, RWJ-57408 (10 μM), blocked the galanin 1-16 (1 μM)-mediated inhibition of voltage-dependent Ca2+ channel. By contrast, the GalR2/GalR3 agonist, galanin 2-11 did not affect the K+-evoked Ca2+ influx in myenteric neurons. GalR1 immunoreactivity was localized solely to myenteric neurons in culture, as previously observed in intact tissue. These findings indicate that the inhibition of depolarization-evoked Ca2+ influx in myenteric neurons in culture is mediated by GalR1 and confirm the presence of functional GalR1 in the myenteric plexus. This is consonant with the hypothesis that GalR1 mediates galanin inhibition of transmitter release from myenteric neurons.

Original languageEnglish (US)
Pages (from-to)1107-1114
Number of pages8
JournalJournal of Neuroscience Research
Volume87
Issue number5
DOIs
StatePublished - 2009

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

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