Gingerols: a novel class of vanilloid receptor (VR1) agonists.
1. Gingerols, the pungent constituents of ginger, were synthesized and assessed as agonists of the capsaicin-activated VR1 (vanilloid) receptor. 2. [6]-Gingerol and [8]-gingerol evoked capsaicin-like intracellular Ca(2+) transients and ion currents in cultured DRG neurones. These effects of gingerols were blocked by capsazepine, the VR1 receptor antagonist. 3. The potency of gingerols increased with increasing size of the side chain and with the overall hydrophobicity in the series. 4. We conclude that gingerols represent a novel class of naturally occurring VR1 receptor agonists that may contribute to the medicinal properties of ginger, which have been known for centuries. The gingerol structure may be used as a template for the development of drugs acting as moderately potent activators of the VR1 receptor.
Dedov
Vadim N
VN
Faculty of Pharmacy, University of Sydney, Sydney, N.S.W. 2006, Australia.
Tran
Van H
VH
Duke
Colin C
CC
Connor
Mark
M
Christie
MacDonald J
MJ
Mandadi
Sravan
S
Roufogalis
Basil D
BD
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002396:Catechols; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005233:Fatty Alcohols / Q000138:chemical synthesis / Q000494:pharmacology*; D016257:Fura-2 / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011955:Receptors, Drug / Q000819:agonists* / Q000502:physiology; D013997:Time Factors
D002396:Catechols; D005233:Fatty Alcohols; D011955:Receptors, Drug; C007845:gingerol; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium; D016257:Fura-2