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Body clock study may bring relief to shift workers and jet-lagged travellers

Charles Arthur,Technology Editor
Wednesday 15 May 2002 19:00 EDT
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The body clock, that curse of shift workers and long-haul airline passengers, may be brought to a standstill after scientists discovered a means of deactivating a protein that plays a key part in its workings.

By blocking the so-called VPAC2 receptor – a group of cells crucial to the functions of the protein – scientists were able to relieve laboratory rats of any of the symptoms of jet lag when their sleep and wake-up times were suddenly adjusted. They appeared to be "clockless".

Professor Tony Harmar, of Edinburgh University's department of neuroscience, who led the research, said VPAC2 was now the target for drug companies working on treatments for humans who had inconvenient body clocks. "Drugs which block the VPAC2 receptor could help adjust the timing of a person's body clock so that normal sleep cycles can be restored," he said. Although the function might seem similar to the hormone melatonin, which some long-haul travellers take to try to speed up their adjustment to jet lag, "melatonin can only adjust your body clock by a certain amount per day, and you have to take it at a particular time".

A drug directed at VPAC2 might leave the body's clocks in effective free-fall, meaning that one could adjust to any degree of time-shift almost at once. The team's research, to be published in the science journal Cell, discovered how messages were relayed in the group of brain cells called the suprachiasmatic nucleus, which control our circadian rhythms – the daily cycles of sleep and of a range of physiological functions.

SCN cells, the team said, must signal to one another using a chemical messenger, a small protein called vasoactive intestinal peptide, for a normal rhythm to be generated. The VPAC2 receptor, which enables cells to respond to this messenger, was unexpectedly identified as a key component of the brain's master clock.

Dr Michael Hastings, of the Medical Research Council Laboratory for Molecular Biology in Cambridge, called for new drugs to help people with sleep disorders. "There is an urgent need for new drugs that act on the biological clock, for the treatment of insomnia, jet lag, and to enable shift workers to function more effectively," he said.

"Now we have identified the genes that make up our body clockwork, the next step is to ask how the clock cells talk to each other and to the rest of the body."

The VPAC2 receptor was also found in other parts of the body such as the pancreas and immune system, but that could work to drug firms' advantage, said Professor Harmar. "Sometimes things developed for one use have a better effect on another – the best example being Viagra."

The anti-impotence pill was originally intended as a heart drug but users found it was ideal for prolonging erections.

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