Buprenorphine inhibits bradykinin-induced release of calcitonin gene-related peptide from rat trigeminal neurons via both mu-opioid and nociceptin/orphanin peptide receptors.
In this study we used the dual opioid and nociceptin/orphanin peptide (NOP) agonist buprenorphine to investigate the relative contributions of opioid and NOP systems in regulating bradykinin-stimulated calcitonin-gene related peptide (CGRP) release from primary cultures of neonatal rat trigeminal neurons. We found that: bradykinin stimulates CGRP secretion either by a direct effect or after applying so-called "bradykinin-priming" protocol. In both cases, buprenorphine was able to inhibit bradykinin-stimulated CGRP secretion; however, inhibition was mediated by NOP receptors when buprenorphine was added to the incubation medium along with bradykinin, whereas it appeared to be mediated by mu-opioid receptors in bradykinin priming experiments. Bradykinin treatments also caused an increase in neuronal prostaglandin production; prostanoids appeared to be involved in the stimulatory effects of bradykinin as well as in buprenorphine inhibition, through apparently unrelated mechanisms.
Capuano
Alessandro
A
Institute of Pharmacology, Catholic University School of Medicine, Largo F. Vito 1, 00168 Rome, Italy.
De Corato
Alice
A
Tringali
Giuseppe
G
Currò
Diego
D
Dello Russo
Cinzia
C
Navarra
Pierluigi
P
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002047:Buprenorphine / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002478:Cells, Cultured; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000502:physiology*; D014276:Trigeminal Nerve / Q000166:cytology; D000094942:Nociceptin Receptor
D000701:Analgesics, Opioid; D001920:Bradykinin; D002047:Buprenorphine; D015740:Calcitonin Gene-Related Peptide; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D000094942:Nociceptin Receptor; C000722285:Oprl1 protein, rat