Evolution of nitric oxide regulation of gut function

Abstract

Although morphologies are diverse, the common pattern in bilaterians is for passage of food in the gut to be controlled by nerves and endodermally derived neuron-like cells. In vertebrates, nitric oxide (NO) derived from enteric nerves controls relaxation of the pyloric sphincter. Here, we show that in the larvae of sea urchins, there are endoderm-derived neuronal nitric oxide synthase (nNOS)-positive cells expressing pan-neural marker, Synaptotagmin-B (SynB), in sphincters and that NO regulates the relaxation of the pyloric sphincter. Our results indicate that NO-dependent pylorus regulation is a shared feature within the deuterostomes, and we speculate that it was a characteristic of stem deuterostomes.

Sea urchin larvae utilize light for regulating the pyloric opening

“…In addition, when the 5HT 2 receptor was knocked down (Fig. 3 c), the pylori of the morphants responded to neither photoirradiation nor serotonin but did respond to the nitric oxide (NO) donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) [ 23 ] (Fig. 3 d, Additional file 1 : Fig.…”

“…S7d). This SNAP experiment was performed because we had recently reported that NO is involved in the pyloric opening in sea urchin larvae, similar to mammals [ 23 ]. The average pyloric opening rates were 4% (control with no treatment), 21.9% (control with photoirradiation), 81.6% (control with serotonin), 93.5% (control with SNAP), 0% (5HT 2 morphants with no treatment), 2.1% (5HT 2 morphants with photoirradiation), 7.5% (5HT 2 morphants with serotonin), and 84.7% (5HT 2 morphants with SNAP).…”

“…S8; see the “ Methods ” section [microinjection of morpholino anti-sense oligonucleotides (MO), mRNAs, and DNA]), suggesting that 5HT 2 is expressed in the stomach. Because the Venus signal representing 5HT 2 expression did not localize to the pylorus but localized everywhere in the stomach, it is likely that serotonin from the anterior neuroectoderm indirectly activates the NO enteric neurons (hereafter referred to as sEN [ 23 ]; Fig. 4 a) and the pyloric sphincter.…”

“…In addition, the functions of sea urchin nervous systems, which are presumptive mediators between photoreception and larval/adult behaviors, have been reported only in a limited number of papers. For example, serotonergic neurons, which are present exclusively in the anterior neuroectoderm, are required for gravity-dependent swimming behaviors [ 22 ], and a nitric oxide (NO) neuron in the pylorus regulates the pyloric opening [ 23 ]. On the other hand, a functional analysis of ciliary band neurons, including recently identified cholinergic neurons [ 24 ], has never been performed [ 25 ], and we do not have any experimental data about the relationship between the nervous system and light stimuli in sea urchins.…”

Biomimetic Engineering of a Scavenger‐Free Nitric Oxide‐Generating/Delivering System to Enhance Radiation Therapy

“…[ 7 ] Analysis of the relevant literature shows that NO also participates in the regulation of various physiological processes, including vascular relaxation, immune regulation, neurotransmission, bone metabolism, among many others. [ 8–13 ]…”