An almost nontoxic tetrodotoxin analog, 5,6,11-trideoxytetrodotoxin, as an odorant for the grass puffer

Abstract

Toxic puffers contain the potent neurotoxin, tetrodotoxin (TTX). Although TTX is considered to serve as a defense substance, previous behavioral studies have demonstrated that TTX acts as an attractive pheromone for some toxic puffers. To elucidate the physiological mechanism of putative pheromonal action of TTX, we examined whether grass puffers Takifugu alboplumbeus can detect TTX. Electroolfactogram (EOG) results suggest that the olfactory epithelium (OE) of grass puffers responded to a type of TTX analog (5,6,11-trideoxyTTX), although it did not respond to TTX. We also examined the attractive action of 5,6,11-trideoxyTTX on grass puffers by recording their swimming behavior under dark conditions. Grass puffers preferred to stay on the side of the aquarium where 5,6,11-trideoxyTTX was administered, and their swimming speed decreased. Additionally, odorant-induced labeling of olfactory sensory neurons by immunohistochemistry against neural activity marker (phosphorylated extracellular signal regulated kinase; pERK) revealed that labeled olfactory sensory neurons were localized in the region surrounding “islets” where there was considered as nonsensory epithelium. 5,6,11-trideoxyTTX has been known to accumulate in grass puffers, but its toxicity is much lower (almost nontoxic) than TTX. Our results suggest that toxic puffers may positively use this TTX analog, which has been present in their body with TTX but whose function was unknown, as an odorant for chemical communication or effective TTX accumulation.

The odor of a nontoxic tetrodotoxin analog, 5,6,11-trideoxytetrodotoxin, is detected by specific olfactory sensory neurons of the green spotted puffers

“…Furthermore, the ovaries of toxic puffers contain both TTX and TDT (Ito et al 2023), and it is believed that they are leaking out from the cloaca (Matsumura 1995). Our previous studies (Noguchi et al 2022;Suzuki et al 2022) and a recent study by Miyazaki et al (2024) demonstrated that both male and female toxic puffers are attracted to TDT. Therefore, these toxic puffers may use TDT odor as a cue to find conspecifics or to feed on TTX-bearing organisms for their efficient toxification.…”

Tetrodotoxins in Tissues and Cells of Different Body Regions of Ribbon Worms Kulikovia alborostrata and K. manchenkoi from Spokoynaya Bay, Sea of Japan

“…Earlier, it was demonstrated that the toxic effect of 5,6,11-trideoxyTTX is minimal [ 43 ], and its contribution to nemertean’s toxicity is ambiguous. A recent behavioral study has reported that 5,6,11-trideoxyTTX elicits chemotaxis of pufferfish Takifugu alboplumbeus and attracts them [ 44 ]. The role of 5,6,11-trideoxyTTX in the communication of nemerteans has not been studied yet.…”

An amphibian toxin phenotype is sexually dimorphic and shows seasonal concordant change between sexes

“…Relative long-range communication is often costly, but readily available molecules can serve a secondary role in mate detection, thereby reducing costs (Rohr et al, 2004;Woodley, 2015). That TTX may serve an ecological role to facilitate reproductive processes and moderate competition between males would not be unusual, as TTX has been found to affect larval newt behavior (Elliott et al, 1993;Zimmer et al, 2006), snail feeding (Hwang et al, 2004), pufferfish mating (Matsumura, 1995;Noguchi et al, 2022), and benthic invertebrate foraging behavior and community dynamics (Bucciarelli and Kats, 2015). The evolution and ecology of TTX has largely focused on its role in chemical defense (Elliott et al, 1993;Gonzalez et al, 1999;Zimmer et al, 2006;Start and De Lisle, 2018), but its complex ecological roles are emerging (Vaelli et al, 2020;Bucciarelli et al, 2021).…”