Ginkgolide B preferentially blocks chloride channels formed by heteromeric glycine receptors in hippocampal pyramidal neurons of rat.
It has been found recently that the platelet activating factor antagonist ginkgolide B is a selective use-dependent blocker of glycine-gated chloride channels. GABAA receptor antagonist picrotoxin is known to block alpha homomeric glycine (Gly) receptors, being less effective for heteromeric alpha1/beta glycine receptors. Studying pyramidal hippocampal neurons of rat, we have confirmed that the effect of picrotoxin depends on the age of the animals. Its blocking ability was characterised by IC50=140+/-12 microM and IC50=354+/-43 microM for 7 and 14 days old rats, respectively, indicating at a possibly increased contribution of heteromeric receptors with animals age. We have revealed that the blocking action of ginkgolide B is subjected to a more drastic change in the same range of ages: the IC50 value is decreased from 1.6+/-0.2 microM for 7 days old rats to 0.27+/-0.01 microM for 14 days old rats. When measured on the background of ginkgolide B (1 microM), IC50 for picrotoxin was 92+/-16 microM. Taken together, these findings indicate that ginkgolide B has higher affinity to heteromeric Gly receptor-gated channels than to the homomeric ones.
Kondratskaya
Elena L
EL
Department of Cellular Membranology, A.A. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Bogomoletz st. 4, Kiev 01024, Ukraine.
Fisyunov
Alexander I
AI
Chatterjee
Shyam S
SS
Krishtal
Oleg A
OA
D000367:Age Factors; D000818:Animals; D018118:Chloride Channels / Q000187:drug effects* / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000378:metabolism*
D018118:Chloride Channels; D004224:Diterpenes; D005343:Fibrinolytic Agents; D018756:GABA Antagonists; D046934:Ginkgolides; D007783:Lactones; D010852:Picrotoxin; D018009:Receptors, Glycine; C045856:ginkgolide B