Analysis of venom from the deadly pit viper may help show the way to regulate blood pressure, writes Dr Claire O'Connell.
The sight of a pit viper poised to bite would send anyone's blood pressure soaring. But the deadly venom delivered by those piercing fangs also holds valuable clues about how our blood pressure is regulated in the body.
Researchers at Queen's University Belfast (QUB) have discovered compounds in snake venom with the potential to both widen and constrict blood vessels. They hope their work will eventually lead to more refined therapies for regulating blood pressure in humans.
Venom is a rich hunting ground for protein compounds that act in a highly specific way in the body, according to Chris Shaw, professor of drug discovery at QUB's school of pharmacy. "Venoms are cocktails of extremely powerful molecules and they have exquisite targeting. We call them the cruise missiles of the protein world," says Shaw, whose research group studies venom from a range of beasts including snakes, frogs, spiders and scorpions. Many established drugs are like carpet bombs - they hit the target but they also cause collateral damage. "But these [ venom] molecules hold the hope of having exquisite, smart-bomb type targeting."
The group works with venom from snakes housed at the Liverpool School of Tropical Medicine. To extract samples they cover a beaker with a plastic film then hold the snake's head so its fangs pierce the film and release into the beaker the thick venom, which has the consistency of golden syrup.
The researchers then purify protein or genetic material from the sample to search for and characterise active compounds that could have therapeutic value. "We try and dissect out what the molecules are, what they do, what their targets are in the body and then we go to work on developing a drug based on that molecule," says Shaw.
One focus of the group has been on venom proteins that affect blood pressure. Venom has a good track record for providing leads for blood-pressure drugs. In the 1940s South American scientists discovered that giving animals a dose of pit viper snake venom increased levels of a substance called bradykinin, which widens blood vessels.
"When people were bitten by this snake their blood pressure fell through the floor, and scientists found that this was due to a group of small peptides which they call bradykinin potentiators," explains Shaw, whose group has also isolated bradykinin potentiators from snake and other venoms.
The original discovery of bradykinins led to the development of blood-pressure-reducing drugs called Ace inhibitors, which block the Ace enzyme that normally breaks down bradykinins in the body.
Shaw's group made the unusual discovery of a bradykinin blocker in venom from three species of pit vipers - the exotically named Mexican moccasin, prairie rattlesnake and South American bushmaster. When they found this new peptide it didn't resemble anything seen before, and they thought it might be another bradykinin potentiator, says Shaw. "So we set up experiments to prove this and were rather shocked when we found it had the opposite effect. It was a bradykinin inhibitor."
It seems contradictory to have a bradykinin inhibitor alongside potentiators in the same blow of venom, but he explains venom is a complex cocktail of chemicals that work in concert. "So what we have probably found is that there may be molecules that act locally and molecules that act centrally to produce these effects."
Their startling discovery has caused them to step back and revise our understanding of blood pressure regulation, an approach that Shaw believes could open routes to discovering new and more refined drug therapies. "Our hope would be to produce the leads for some new medicine, maybe some more effective Ace inhibitors, or inhibitors for other enzymes that are involved in blood pressure regulation or other processes."