Regulation of calcitonin gene-related peptide release from rat trigeminal nucleus caudalis slices in vitro.
Calcitonin gene-related peptide (CGRP) released from trigeminal primary afferents has been implicated in the pathophysiology of migraine. Here, we have used an in vitro slice preparation to investigate its release from nerve terminals in the rat trigeminal nucleus caudalis. Extracellular-calcium dependent CGRP release was stimulated by both capsaicin and neuronal depolarization with KCl. The capsaicin (1 microM)-evoked CGRP release was blocked by capsazepine and was also attenuated in the presence of the cyclooxygenase inhibitor, indomethacin, an effect that was reversed when slices were stimulated with capsaicin in the presence of the cyclooxygenase metabolite, prostaglandin E(2). Taken together, these data further highlight the importance of prostaglandins as enhancers of neuropeptide release and suggest that CGRP released from the central terminals of trigeminal neurones has the potential to be involved in the transmission of nociceptive information of relevance to migraine headache.
Neurology Centre of Excellence for Drug Discovery, GlaxoSmithKline, Cold Harbour Road, Harlow, Essex CM 19 5AW, UK. david.jenkins@astrazeneca.com
David W
DW
Jenkins
Christopher J
CJ
Langmead
Andrew A
AA
Parsons
Paul J
PJ
Strijbos
D000704:Analysis of Variance; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014275:Trigeminal Caudal Nucleus / Q000378:metabolism*
D016861:Cyclooxygenase Inhibitors; D011189:Potassium Chloride; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium; D007213:Indomethacin