A small molecule screen identifies novel inhibitors of mechanosensory nematocyst discharge in Hydra

Cnidarians are characterized by the possession of stinging organelles, called nematocysts, which they use for prey capture and defense. Nematocyst discharge is controlled by a mechanosensory apparatus with analogies to vertebrate hair cells. Members of the transient receptor potential (TRPN) ion channel family are supposed to be involved in the transduction of the mechanical stimulus. A small molecule screen was performed to identify compounds that affect nematocyst discharge in Hydra. We identified several [2.2]paracyclophanes that cause inhibition of nematocyst discharge in the low micro-molar range. Further structure-activity analyses within the compound class of [2.2] paracyclophanes showed common features that are required for the inhibitory activity of the [2.2] paracyclophane core motif. This study demonstrates that Hydra can serve as a model for small molecule screens targeting the mechanosensory apparatus in native tissues.

Automated summary

Cnidarians possess stinging organelles called nematocysts for prey capture and defense, controlled by a mechanosensory apparatus similar to vertebrate hair cells. A study identified [2.2]paracyclophanes as compounds that inhibit nematocyst discharge in Hydra, demonstrating the potential of using Hydra as a model for small molecule screens targeting mechanosensory apparatus in native tissues.