Nociceptin (1-13)NH2 inhibits stimulated calcitonin-gene-related-peptide release from primary cultures of rat trigeminal ganglia neurones.
In this work we have developed and characterized primary cultures of neonatal rat trigeminal ganglia neurones; calcitonin-gene-related-peptide (CGRP) released from cells was taken as a marker of neuronal function. A significant and consistent increase in CGRP secretion was elicited by non-specific (56 mm KCl or veratridine) or specific (capsaicin) depolarizing stimuli. This paradigm was subsequently used to investigate the effects of nociceptin, an opioid-like peptide involved in central and peripheral control of nociception. We found that the nociceptin analogue nociceptin (1-13)NH2 (NOC) did not affect baseline CGRP release, but it reduced in a concentration-dependent manner CGRP release induced by all tested stimuli. NOC-induced reduction was statistically significant from 0.01 nm onward and achieved maximal effects at 10 nm. Such effects of NOC were seemingly mediated by the activation of specific ORL1 receptors, as a well-known nociceptin antagonist, N(Phe1)nociceptin (1-13)NH2, was able to completely revert NOC inhibition of capsaicin-stimulated CGRP release.
Capuano
A
A
Department of Neuroscience and Institute of Pharmacology, Catholic University Medical School, Rome, Italy.
Currò
D
D
Dello Russo
C
C
Tringali
G
G
Pozzoli
G
G
Di Trapani
G
G
Navarra
P
P
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D015740:Calcitonin Gene-Related Peptide / Q000187:drug effects / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D007118:Immunoassay; D007150:Immunohistochemistry; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018847:Opioid Peptides / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D018712:Analgesics, Non-Narcotic; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722285:Oprl1 protein, rat