LOW-AFFINITY OF FMRFAMIDE AND 4 FARPS (FMRFAMIDE-RELATED PEPTIDES), INCLUDING THE MAMMALIAN-DERIVED FARPS F-8-FAMIDE (NPFF) AND A-18-FAMIDE, FOR OPIOID-MU, OPIOID-DELTA, OPIOID-KAPPA(1), OPIOID-KAPPA(2A), OR OPIOID-KAPPA(2B) RECEPTORS

The binding affinities at opioid receptor subtypes in rat or guinea pi g brain membranes were determined for the neuropeptide FMRFamide (Phe- Met-Arg-Phe-NH2), the two mammalian-derived FMRFamide-related peptides F-8-Famide (NPFF; Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) and A-18-Famid e -Pro-Phe-Trp-Ser-Leu-Ala-Ala-Pro-Gln-Arg-Phe-NH2), and the two other FMRFamide-related peptides Tyr-Phe-Met-Arg-Phe-NH2 (Tyr-FMRFamide) an d Pro-Gln-Arg-Phe-NH2, (Pro-Gln-RFamide). The mu and delta sites were labeled in rat brain membranes using tritiated [D-Ala(2),N-MePhe(4),Gl y-ol(5)]enkephalin ([H-3]DAMGO) and [D-Ala(2),D-Leu(5)]enkephalin ([H- 3]DADLE), respectively. The kappa sites were labeled in guinea pig bra in using [H-3]U-69,593 after treatment with BIT and FIT for kappa(1) a nd [H-3]bremazocine after pretreatment with BIT and FIT for kappa(2). The kappa(2a) binding sites were assayed using [Leu(5)]enkephalin to b lock kappa(2b) sites and the kappa(2b) sites were assayed using (-)-(1 S,2S)-U50,488 to block kappa(2a) sites. Neither FMRFamide nor any of t he FMRFamide-related peptides (up to 61.0 mu M) displayed significant affinity at any of the subtypes of opioid receptor. Hence, the known a bility of FMRFamide and FaRPs to interact with the opioid system does not appear to be related to direct binding to these opioid receptors.