The neuroprotective kappa-opioid CI-977 alters glutamate-induced calcium signaling in vitro.
The effect of the neuroprotective kappa opioid agonist CI-977 on glutamate (GLU)-stimulated calcium signaling was studied in individual primary rat cortical neurons. Using laser scanning confocal microscopy and the fluorescent calcium probe fluo-3, both the sustained and biphasic intracellular calcium concentration [Ca2+]i changes induced by GLU (20-40 microM) were altered by CI-977 (25-100 nM), thereby shifting the neuronal population response from unbuffered to buffered patterns of [Ca2+]i flux. This effect was consistent with the previously demonstrated neuroprotective action of CI-977 against glutamate toxicity in vitro. The effect of CI-977 in altering GLU-induced [Ca2+]i signaling was attenuated by naloxone, consistent with a neuroprotective action of CI-977 at opioid receptors, presumably of the kappa subtype.
DeCoster
M A
MA
Louisiana State University Medical Center, Neuroscience Center, New Orleans 70112-2234.
Conover
J R
JR
Hunter
J C
JC
Tortella
F C
FC
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D018846:Excitatory Amino Acids / Q000037:antagonists & inhibitors; D018698:Glutamic Acid / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009994:Osmolar Concentration; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D015398:Signal Transduction / Q000187:drug effects*
D001572:Benzofurans; D018846:Excitatory Amino Acids; D018696:Neuroprotective Agents; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D018698:Glutamic Acid; C067110:enadoline; D002118:Calcium