Prostaglandins and neuropeptides in rat trigeminal neurones

• Main Author: Jenkins, D. W.
• Published: University of Cambridge 2003
• Subjects: 616.8
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.605089

Having identified prostaglandin receptors in trigeminal tissue, the functional effects of prostaglandin receptor ligands on CGRP release were investigated using cultured adult rat trigeminal ganglion neurones as a model system. It was found that calcium-dependent CGRP release could be stimulated following stimulation of DP, EP and IP receptors. Furthermore, the use of EP receptor specific agonists and antagonists suggested that the EP receptor subtype involved might be the EP₂ receptor. The effects of several agents on prostaglandin E₂ (PGE₂) release from the cultured rat trigeminal neurones were also evaluated. From these data it was concluded that PGE₂ itself could be released in a p42/p44 MAP kinase and protein kinase C-dependent manner following treatment with the algesic peptide, bradykinin, but not after depolarisation or treatment with either capsaicin or CGRP. Finally, superfusion studies were conducted to measure CGRP release from TNC slices <i>in vitro</i>. In this experimental model it was found that calcium-dependent CGRP release was stimulated by depolarisation and capsaicin treatment. Furthermore, evidence was obtained to suggest that although exogenous prostaglandins did not cause CGRP release <i>per se</i> in this system, they were able to modulate chemically stimulated CGRP release. In summary, this study has shown: (1) the presence of EP and IP prostanoid receptors in rat trigeminal ganglia, (2) that CGRP is released from cultured trigeminal neurones following DP, EP and IP receptor activation, (3) that PGE₂ is released by bradykinin from the same neuronal cultures and (4) that CGRP release from TNC neurones is also prostaglandin-sensitive. Taken together, these data provide further evidence for important roles of both prostaglandins and CGRP in the pathophysiology of migraine headache.