Neuropeptide FF selectively attenuates the effects of nociceptin on acutely dissociated neurons of the rat dorsal raphe nucleus.
Intracellular Ca2+ concentration ([Ca2+]i) was measured in neurons, acutely dissociated from the rat dorsal raphe nucleus (DRN), with the fluorescent calcium probe Fluo3. Nociceptin (300 nM) had no effect on resting [Ca2+]i but reduced the magnitude of the [Ca2+]i transient triggered by depolarization in 90% of neurons having polygonal or fusiform perikarya. In 94% of neurons with the same morphology 5-HT (30 microM) also reduced the magnitude of the [Ca2+]i transient. The selective 5-HT(1A) receptor antagonist 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-ben zamide hydrochloride (p-MPPI) (0.4 microM) strongly attenuated (by 72+/-7%, n=4) this effect. The responses to nociceptin and 5-HT were not affected by BaCl2 (100 microM). The neuropeptide FF analog [D-Tyr1, (N-Me)Phe3]NPFF (1DMe) altered neither the resting [Ca2+]i nor the [Ca2+]i transient triggered by depolarization but dose-dependently decreased the effect of nociceptin (EC50=1.8 nM, maximal reduction: 68+/-5%). 1DMe had no effect on the response to 5-HT. Another neuropeptide FF analog, exhibiting a different pharmacological activity in mice and rats, [D-Tyr1, D-Leu2, D-Phe3]NPFF (1 microM) also reduced the effect of nociceptin by 74+/-11% (n=4). Few neurons (5 out of 42), either with polygonal/fusiform or smaller ovoid cell bodies, responded to the mu-opioid receptor agonist [D-Ala2, (N-Me)Phe4, Gly-ol5]-enkephalin (DAGO) with a decrease in the depolarization-induced [Ca2+]i transient. 1DMe (100 nM) attenuated this response by 69+/-14%. These results suggest that, at the cellular level, neuropeptide FF selectively counteracts the effects of opioid receptor activation.
Roumy
M
M
Institut de Pharmacologie et de Biologie Structurale, C.N.R.S. UPR 9062, 205 Route de Narbonne, 31077, Toulouse, France. roumy@ipbs.fr
Zajac
J
J
D000631:Aminopyridines / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D066298:In Vitro Techniques; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009474:Neurons / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D018847:Opioid Peptides / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*; D000097629:Nociceptin
D000631:Aminopyridines; D000701:Analgesics, Opioid; D017609:Barium Compounds; D002118:Calcium; D002712:Chlorides; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009292:Narcotic Antagonists; D009842:Oligopeptides; D018847:Opioid Peptides; D010879:Piperazines; D017450:Receptors, Opioid, mu; D012701:Serotonin; D012702:Serotonin Antagonists; D014665:Vasodilator Agents; D000097629:Nociceptin; C024986:barium chloride; C080757:tyrosyl-leucyl-N-methylphenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; C087205:4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide