|Budget Amount *help
¥2,300,000 (Direct Cost : ¥2,300,000)
Fiscal Year 1997 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1996 : ¥1,500,000 (Direct Cost : ¥1,500,000)
The anaticipated role of "antiopiates", which believe to modulate endogenous pain inhibitory system, is still unclear ; both the anti-analgesic effect of Tyr-MIF-1 (Tyr-Pro-Leu-Gly amide), one of the antiopiate candidate, and its derivativ, YPIG (Tyr-Pro-Ile-Gly amide), and the effect of these peptides on emotionallity and leaning/memory processes, were investigated in mice.
Tyr-MIF-1, when administered intraperetoneally (i.p.) or intrathecally, significantly attenuated the antinociceptive effect of both morphine and U-50488, mu and kappa opioid receptor agonist, respectively, but the peptide given intracerebroventricularly (i.c.v.) had no effect on these antinociceptive effects. Tyr-MIF-1 given i.p. but not i.c.v.also inhibited antinociception induced by DPDPE,a delta receptor agonist. I.c.v.YPIG potetiated morphine analgesia while leaving antinociception by U-50,488H unaffected.
Tyr-MIF-1 suppressed not only footshock (FS) - and socio-psychological (PSY)- stress-induced analgesia (SLA)
, both are naloxone reversible, but also naloxone insensitive forced swim (SW) -SIA.YPIG given i.p.blocked FS- and PSY-SLA ; however, i.c.v.YPIG augmented antinociception induced by FS-, PSY- and SW-stress.
The suppressive effect of FS- and PSY-stress on the development of morphine tolerance was extinguished by Tyr-MIF-1 and YPIG given i.p.
Tyr-MLF-1 increased time spent open arm in the elevated plus maze test, suggesting anxiolytic properties of the peptide.
Tyr-MIF-1 had no effect on the learning/memory precesses in one trial passive avoidance test.
In experiment of mu opioid receptor binding assay, the affinity of Tyr-MIF-1 was about five times lower than that of YPIG.
Taken together, these results imply the inclusive involvement of Tyr-MIF-1 in the modulation of the adaptive mechanisms, including pain-inhibitory systems and emotionality. The stereospecific structure seems required for the production of anitopiate effect of Tyr-MIF-1, from the distinct effects induced by Tyr-MIF-1 and YPIG.
In addition, the physiological and pharmacological role of another candidate of antlopiates, complement C3a, is now undertaken to clarify. Less