PRONOCICEPTIVE EFFECTS OF THE NEUROPEPTIDE, NOCICEPTIN, IN THE LAND SNAIL, CEPAEA-NEMORALIS

The peptide, Phe-Gly ly-Ala-Arg-Lys-Ser-Ala-Arg-Lys-Leu-Ala-Asn-Gln-OH , recently isolated from rat brain, has been suggested to be an endoge nous agonist for an orphan, opioid-like receptor (ORL(1)). This peptid e, called ''nociceptin'' (or orphanin FQ), has been su,ggested to have pronociceptive, hyperalgesic functions. The present study examined th e effects of nociceptin aversive thermal (nociceptive) responses in an invertebrate, the land snail, Cepaea nemoralis. Nociceptin had signif icant, dose-related pro-nociceptive effects in Cepaea, whereas the opi oid peptide, dynorphin A, which shares some sequence similarities with nociceptin, had significant antinociceptive effects. The effects of d ynorphin were blocked by the kappa-opiate receptor antagonist, nor-bin altorphimine, whereas those of nociceptin were unaffected. Repeated da ily administrations of nociceptin resulted in reduced pronociceptive e ffects, suggestive of the development of tolerance to the hyperalgesic actions of this opioid-related peptide. These findings suggest that t he novel peptide, nociceptin, can influence nociceptive responses in t he snail, Cepaea, in a manner similar to that indicated for rodents.