GABA, acting at both GABAA and GABAB receptors, inhibits the release of cholecystokinin-like material from the rat spinal cord in vitro.
Superfusion of slices of the dorsal zone of the lumbar enlargement of the rat spinal cord with an artificial cerebrospinal fluid allowed the collection of cholecystokinin-like material (CCKLM) whose Ca(2+)-dependent release could be evoked by tissue depolarization with 30 mM K+. Studies on the possible influence of GABA and related agonists on this process showed that the amino acid, the GABAA agonist, muscimol, and the GABAB agonist, baclofen, inhibited the K(+)-evoked release of CCKLM from the rat spinal cord in a concentration-dependent manner. Maximal inhibition did not exceed -40% with either agonist. Furthermore, the effects of GABAA and GABAB receptor stimulation were not additive. Whereas the effects of muscimol (10 microM) and baclofen (1 microM) could be completely antagonized by bicuculline (1 microM) and phaclofen (10 microM), respectively, complete blockade of the inhibition by GABA (1 microM) could only be achieved in the presence of both antagonists. These data indicate that both GABAA and GABAB receptors are involved in the negative influence of GABA onto CCK-containing neurones within the dorsal horn of the rat spinal cord. Apparently, these receptors are not located on CCK-containing neurones themselves, since the inhibitory effect of GABA on the K(+)-evoked release of CCKLM could be completely prevented by tetrodotoxin (1 microM). As CCK acts centrally as an endogenous opioid antagonist, such a GABA-inhibitory control of spinal CCK-containing neurones might participate in the analgesic action of the amino acid via the intrathecal route.
Benoliel
J J
JJ
INSERM U 288, Neurobiologie Cellulaire et Fonctionnelle, Paris, France.
Bourgoin
S
S
Mauborgne
A
A
Pohl
M
M
Legrand
J C
JC
Hamon
M
M
Cesselin
F
F
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002766:Cholecystokinin / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D066298:In Vitro Techniques; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D010477:Perfusion; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D011963:Receptors, GABA-A; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D002766:Cholecystokinin; D001418:Baclofen