New research paves the way for a contraction-inhibiting drug that may help to prevent preterm labor.
The "love hormone" is naturally released in our body when we make love or make new friends. But apart from its role in social bonding and reproduction, oxytocin also helps mothers give birth.
Oxytocin stimulates powerful contractions during labor, helping the cervix to open up in preparation for delivery. This is why it is often used as a drug to aid birth.
Vasopressin also plays an important role during birth. The hormone is believed to have analgesic effects, as during natural delivery its levels increase extremely sharply.
A new study - led by researchers from the Medical University of Vienna in Austria - examines how the two hormones work in both insects and humans. The research also explores the therapeutic effect of a synthetic equivalent of the two hormones.
The study was published in the journal Scientific Reports.
Insect neuropeptide inhibits uterine contractions
The team of international researchers - led by Christian Gruber from the Institute of Pharmacology at Medical University of Vienna - set out to isolate a neuropeptide from ants that is structurally very similar to oxytocin and vasopressin.
Neuropeptides are one of the two major classes of neurotransmitters, and both vasopressin and oxytocin are neuropeptides.
Insects also have neuropeptides, and Gruber and team isolated one called inotocin - which is the equivalent of vasopressin and oxytocin in arthropods.
Researchers then created a synthetic equivalent of inotocin, which enabled them to better understand how the biochemical signaling process of oxytocin and vasopressin works.
Vasopressin typically controls the water balance through the kidneys, but in combination with oxytocin, it regulates the blood supply to the uterus during childbirth. Like oxytocin, vasopressin also stimulates contractions during delivery.
So far, medical scientists have identified four brain receptors that respond to the two neuropeptides: one oxytocin receptor (OTR) and three vasopressin receptors (VR) - VR1a, VR1b, and VR2.
Then, using a unique strategy for the discovery of ligands, researchers isolated inotocin from the black garden ant, cloned its cognate receptor, and examined its pharmacological effect on both the insect and the human OTRs and VRs.
Ligands are "any atom or molecule attached to a central atom" in a complex chemical compound.
In humans, researchers found that inotocin activated the V1b receptor, but inhibited the V1a. Then, Gruber and team tested the inotocin ligand on human uterine tissue, and found that it successfully inhibited muscular contractions.
"Surprisingly, by introducing a small chemical modification into this insect neuropeptide, we were able to develop a very stable and highly selective inhibitor of the human vasopressin V1a receptor," explains Gruber. "This ligand was tested on human uterine tissue and effectively inhibited muscular contractions. Further tests are now necessary to explore clinical applications of the active lead molecule."
Significance of the study
The research used a unique strategy that took advantage of millions of years of evolution, to which we owe the structural similarities between humans and insects.
"In a parallel study, by analyzing genetic data sets, we have now been able to show that many insects have an oxytocin or vasopressin-like signaling system, and it is presumably functionally related throughout the animal kingdom," explains Gruber.
Specifically, the oxytocin-vasopressin signaling system has been around for approximately 600 million years, and being able to compare their receptors at a molecular level may enable scientists to develop new drugs and therapies.
For instance, an oxytocin-vasopressin receptor inhibitor could prevent unwanted uterine contractions in preterm labor.
The study's lead author also emphasizes the contribution of the research:
"Our concept is innovative and fascinating: take an insect neuropeptide, skip over approximately 600 million years of evolution and, with a small chemical modification, this substance may be suitable to act as a drug candidate for use in humans. It is equally important to utilize these new molecules as research 'tools.' Only by developing receptor subtype-selective ligands, it will be possible to investigate the biochemical principles of such complex signaling systems."