Evidence for an excitatory action of the benzodiazepine receptor inverse agonist FG 7142 on C-fibre afferents.
(1) The stimulation of adrenocorticotrophic hormone (ACTH) release by FG 7142 was found to be 50% inhibited in capsaicin-desensitized rats indicating that the excitatory effect of this inverse benzodiazepine agonist is partly mediated through capsaicin-sensitive afferents. (2) The in vitro release of substance P from spinal cord slices was stimulated in a tetrodotoxin-resistant manner by FG 7142. No stimulation of the substance R release by FG 7142 was observed when spinal cord slices were taken from capsaicin-pretreated rats which lack afferent C-fibres. (3) Ro 15-1788 antagonized the in vivo as well as the in vitro stimulatory effects of FG 7142 indicating that they were brought about by interaction with benzodiazepine receptors. (4) It is concluded that FG 7142 has a direct excitatory effect on central terminals of capsaicin-sensitive afferents and that neurotransmitters released from primary afferents are involved in inducing ACTH release following administration of FG 7142 in vivo.
Donnerer
J
J
Institut für Experimentelle und Klinische Pharmakologie, Universität Graz, Austria.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D005260:Female; D005442:Flumazenil / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects*; D009475:Neurons, Afferent / Q000187:drug effects; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000378:metabolism
D002243:Carbolines; D011963:Receptors, GABA-A; D013373:Substance P; D005442:Flumazenil; C035874:FG 7142; D000324:Adrenocorticotropic Hormone