While working with Kosterlitz at Aberdeen, Hughes helped discover the enkephalinpeptides. Kosterlitz had developed assays for responses to opiate drugs, using pieces of guinea pigintestine and mousevas deferens.[7] Hughes sought to determine whether molecules present in brains could mimic the effects of the drugs. Reflecting in 1995 about that time, Hughes said: "From my personal point of view, I think that the reason I got interested in searching for an endogenous opioid-like substance is that I had been previously involved during my PhD student work in looking at non-adrenergic, noncholinergic innervation of various blood vessels and that's what my PhD thesis was
eventually written on."[10] He would bicycle daily to a slaughterhouse, where he would trade bottles of whiskey to the butchers in exchange for pig heads, and he subsequently prepared brain extracts using acetone.[9] After testing many samples in Kosterlitz's assays, the two scientists were able to isolate and identify two peptides, met- and leu-enkephalin, as naturally occurring molecules from the brain, that have activity resembling opioids.[6][9] Hughes and Kosterlitz first announced their findings at a scientific conference in May 1974, and published the structures of the two enkephalins in 1975.[8][11] In 1978, they shared the Lasker award with Solomon H. Snyder, and Hughes in particular was credited with predicting the existence of endogenous opioids.[5]
References
^Marshall, Fiona (1990). Cholecystokinin/dopamine interactions in the rat basal ganglia (PhD thesis). University of Cambridge. EThOSuk.bl.ethos.386170.
^Hughes, J.; Smith, T.W.; Kosterlitiz, H.W.; Fothergill, Linda A.; Morgan, B.A.; Morris, H.R. (18 December 1975). "Identification of two related pentapeptides from the brain with potent opiate agonist activity". Nature. 258 (5536): 577–579. Bibcode:1975Natur.258..577H. doi:10.1038/258577a0. PMID1207728. S2CID95411.