d-ala(2)-mephe(4)-met(0)-ol-enkephalin and tifluadom

The analgesic effects of mu- and kappa-opioid agonists, including morphine, FK33,824, U50,488H, tifluadom and bremazocine, have been determined in C57BL/6J-bgJ (beige) and CXBK mice which are hyporesponsive to mu-opioid receptor-mediated analgesia compared with those of control mice (C57BL/6J (C6J), C57BL/6By (C6By), BALB/cBy (BALB] using an abdominal constriction assay. The analgesic effect of subcutaneously administered morphine and FK33,824 in both beige and CXBK mice was significantly reduced compared with the controls and the analgesic effect of U50,488H and tifluadom in beige mice was significantly reduced compared with the wild strain (C6J). No reduction of analgesic effect of U50,488H and tifluadom was seen in CXBK compared with its progenitor strains, C6By and BALB, except for a reduction of the effect of tifluadom in CXBK compared with C6By. There was no strain difference in the bremazocine-induced analgesia. These results suggest that the beige mouse has a deficit in analgesia mediated by both mu- and kappa-opioid receptors, whereas the CXBK is deficient only in the mu-opioid receptor-mediated analgesia.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Acetates; Acetic Acid; Analgesics; Animals; Benzodiazepines; Benzomorphans; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Female; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred Strains; Morphine; Narcotics; Pyrrolidines; Receptors, Opioid; Receptors, Opioid, kappa; Receptors, Opioid, mu

Using an in-vitro superfusion system, the relative importance of three distinct subtypes of the opiate receptor in the control of the secretion of LHRH from the mediobasal hypothalamus of the cockerel was investigated. Basal release of LHRH was increased by the antagonist naloxone, which shows some mu-receptor selectivity, in a manner which was reversed by the mu-receptor specific agonist [D-Ala2, N-Phe4-Gly-ol5]-enkephalin (DAGO) and the mu- and delta-specific agonist [D-Ala2,N-Phe4,Met(0)ol5]-enkephalin (FK 33-824). The delta-specific agonist [D-Thr2,L-Leu5]-enkephalyl-Thr (DTLET) and the kappa-specific agonist 1-methyl-2(3-thienylcarbonyl)-aminomethyl-5-(2-fluorophenyl)-H-2, 3-dihydro-1,4-benzodiazepine (KC 6128; (+)-titfluadom) did not reverse the effect of naloxone. The delta-specific antagonist N,N-diallyl-Tyr-alpha-aminoisobutyricacid-Phe-Leu-OH (ICI 174,864) failed to influence basal release. Release of LHRH stimulated by increasing the potassium ion concentration of the superfusate to 48 mmol/l was reduced by DAGO in a manner which was reversed by naloxone, and by FK 33-824 in a manner which was reversed by both naloxone and ICI 174,864. The agonists DTLET and titfluadom did not affect stimulated release of LHRH. These results support the proposal that spontaneous release of LHRH is tonically inhibited by agonists acting through the mu-receptor whilst, in response to a stimulus, the delta-receptor, in addition to the mu-receptor, may be involved.

Topics: Animals; Benzodiazepines; Chickens; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine; Enkephalins; Gonadotropin-Releasing Hormone; Hypothalamus; In Vitro Techniques; Male; Naloxone; Oligopeptides; Receptors, Opioid