Abstract
Background and AimsCortistatin (CST) is a novel neuropeptide with high structural homology with somatostatin. We previously found that CST is expressed by enteric neurons and acts as an inhibitory neurotransmitter in the submucosal plexus. The aim of the present study was to evaluate the effect of CST on neurogenic intestinal secretion.MethodsSubmucosal/mucosal preparations from guinea pig ileum were mounted in Ussing flux chambers for measurement of short‐circuit current (Isc) as an indicator of mucosal secretion. Transmural electrical field stimulation (EFS) was used to evoke neural‐mediated intestinal secretion.ResultsApplication of CST‐14 (rat), CST‐17 (human), CST‐29 (rat), or CST‐29 (human) to the submucosal side of the preparation decreased baseline Isc in a concentration‐dependent manner with an IC50 (in nM) of 90.5, 52.1, 102.9 or 71.6, respectively. The somatostatin‐2 receptor (SSTR‐2) antagonist CYN 154806 significantly suppressed CST‐14r, CST‐17h, CST‐29r, or CST‐29h‐evoked ΔIsc. The neuronal blocker tetrodotoxin significantly reduced CST‐14r, CST‐17h, CST‐29r, or CST‐29h‐evoked ΔIsc. CSTs produced a concentration‐dependent reduction of the EFS‐evoked secretory responses, which was antagonized by CYN 154806. Immunoreactivity (IR) of CST‐17 was found in submucosal neurons. CST‐17‐IR was localized in cholinergic secretomotor neurons but was absent from non‐cholinergic secretomotor neurons.ConclusionsThe results suggest that CSTs act at SST‐2 receptors in the submucosal plexus to suppress secretomotor neuronal excitability and neurogenic intestinal secretion.
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