- 8 Z , 1 1 Z , 1 4 Z - e icos atri eno ic ▁acid ▁( 4 , 5 - E ET ) ▁made ▁by ▁the ▁met abol ism ▁of ▁a rach id onic ▁acid ▁by ▁any ▁one ▁of ▁several ▁cy to chrome ▁P 4 5 0 ▁en zym es ▁( see ▁E po xy e icos atri eno ic ▁acid ) ▁like wise ▁directly ▁activ ates ▁TR PA 1 ▁to ▁ampl ify ▁pain ▁per ception . ▁ ▁Studies ▁with ▁m ice , ▁gu inea ▁p ig , ▁and ▁human ▁t issues ▁and ▁in ▁gu inea ▁p igs ▁indicate ▁that ▁another ▁a rach id onic ▁acid ▁met abol ite , ▁Pro stag land in ▁E 2 , ▁oper ates ▁through ▁its ▁prost ag land in ▁EP 3 ▁G ▁protein ▁couple d ▁re ceptor ▁to ▁trigger ▁c ough ▁responses . ▁Its ▁mechanism ▁of ▁action ▁does ▁not ▁appear ▁to ▁involve ▁direct ▁binding ▁to ▁TR PA 1 ▁but ▁rather ▁the ▁indirect ▁activation ▁and / or ▁sens it ization ▁of ▁TR PA 1 ▁as ▁well ▁as ▁TR P V 1 ▁re cept ors . ▁Gen etic ▁polym orphism ▁in ▁the ▁EP 3 ▁re ceptor ▁( rs 1 1 2 0 9 7 1 6 ), ▁has ▁been ▁associated ▁with ▁A CE ▁in hib itor - indu ce ▁c ough ▁in ▁humans . ▁ ▁More ▁recently , ▁a ▁pe pt ide ▁to x in ▁term ed ▁the ▁was abi ▁re ceptor ▁to x in ▁from ▁the ▁Australian ▁black ▁rock ▁sc orp ion ▁( U rod