gamma-Aminobutyric acid, through GABAA receptors, inhibits the potassium-stimulated release of calcitonin gene-related peptide- but not that of substance P-like material from rat spinal cord slices.
Superfusion of slices of the dorsal zone of the lumbar enlargement with an artificial cerebrospinal fluid was used to investigate the possible modulation by GABA receptor ligands of the in vitro release of calcitonin gene-related peptide- and substance P-like materials (CGRPLM and SPLM) from the rat spinal cord. Whereas the spontaneous outflow of both peptides remained unaffected, the K+ (30 mM)-evoked overflow of CGRPLM could be partially inhibited (approx. -30%) by GABA (1 microM-0.1 mM) and muscimol (10 microM-0.1 mM) but not by baclofen (1-10 microM). Bicuculline methiodide (1 microM) completely prevented the inhibition by GABA (1 microM) and muscimol (10 microM) as expected from an action through GABAA receptors. By contrast, the K(+)-evoked SPLM overflow was altered neither by GABA nor muscimol and baclofen. These data further support that GABA exerts a presynaptic inhibitory control of (CGRP-containing) primary afferent fibres within the rat dorsal horn.
Bourgoin
S
S
INSERM U288, Neurobiologie Cellulaire et Fonctionnelle, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Pohl
M
M
Benoliel
J J
JJ
Mauborgne
A
A
Collin
E
E
Hamon
M
M
Cesselin
F
F
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009118:Muscimol / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D011963:Receptors, GABA-A; D009118:Muscimol; D013373:Substance P; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D015740:Calcitonin Gene-Related Peptide; D011188:Potassium; D001640:Bicuculline