title: (S)-AMPA inhibits electrically evoked calcitonin gene-related peptide (CGRP) release from the rat dorsal horn: reversal by cannabinoid receptor antagonist SR141716A.
abstract: Previous studies in the hippocampus and cerebellum demonstrate that depolarisation of postsynaptic neurones stimulates the rapid synthesis and release of an endocannabinoid that retrogradely interacts with pre-synaptic CB(1) to modulate neurotransmitter release. This study evaluated whether depolarisation of second order neurones in the dorsal horn of the spinal cord by the AMPA receptor agonist, (S)-AMPA, would modulate sensory neurotransmission via release of endocannabinoids. Using an isolated rat dorsal horn with dorsal root attached in vitro preparation the release of calcitonin gene-related peptide (CGRP) after electrical stimulation of the dorsal roots was measured. Superfusion of either WIN55,212-2 (1 microM) or (S)-AMPA (1 microM) significantly attenuated CGRP release in a CB(1)-dependent manner (SR141716A, 5 microM). This provides indirect pharmacological evidence for an AMPA-evoked release of endogenous cannabinoids inhibiting peptide release from primary afferent neurons. This study confirms that CGRP release from the dorsal horn is modulated via CB(1) activation. Furthermore a depolarising stimulus also modulates CGRP release, potentially via the release of endogenous cannabinoids.
authors.affiliation: Pain Research Group, Department of Anaesthetics, Faculty of Medicine, Imperial College, London SW109NH, UK.
authors.forename: J W
authors.initials: JW
authors.lastname: Brooks
authors.forename: S W N
authors.initials: SW
authors.lastname: Thompson
authors.forename: A S C
authors.initials: AS
authors.lastname: Rice
authors.forename: M
authors.initials: M
authors.lastname: Malcangio
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D063387:Cannabinoid Receptor Antagonists; D004558:Electric Stimulation / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid / Q000378:metabolism; D000077285:Rimonabant; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology*
chemical_list: D063387:Cannabinoid Receptor Antagonists; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D015740:Calcitonin Gene-Related Peptide; D000077285:Rimonabant