Endomorphin analogues containing D ‐Pro 2 discriminate different μ‐opioid receptor mediated antinociception in mice

The antagonistic actions of D ‐Pro 2 ‐endomorphins on inhibition of the paw withdrawal response by endomorphins were studied in mice. D ‐Pro 2 ‐endomorphin‐1 and D ‐Pro 2 ‐endomorphin‐2, injected intrathecally (i.t.), had no significant effect on the nociceptive thermal threshold alone. When D ‐Pro 2 ‐endomorphin‐1 (0.05–0.1 pmol) was injected simultaneously with i.t. endomorphin‐1 (5.0 nmol) or endomorphin‐2 (5.0 nmol), antinociception induced by endomoprhin‐1 was reduced significantly, whereas endomorphin‐2‐induced antinociception was not affected by D ‐Pro 2 ‐endomorphin‐1. Antinociception induced by i.t. endomorphin‐2 (5.0 nmol) was reduced significantly by its analogue, D ‐Pro 2 ‐endomorphin‐2 (100 pmol), but not by D ‐Pro 2 ‐endomorphin‐1. D ‐Pro 2 ‐endomorphin‐1. D ‐Pro 2 ‐endomorphin‐1 also antagonized the antinociceptive effect of i.t. DAMGO, a μ‐opioid receptor agonist, whereas D ‐Pro 2 ‐endomorphin‐2 failed to reduce the effect of DAMGO. These results suggest that endomorphin analogues containing D ‐Pro 2 are able to discriminate the antinociceptive actions of μ 1 ‐ and μ 2 ‐opioid receptor agonists at the spinal cord level. British Journal of Pharmacology (2002) 137 , 1143–1146. doi: 10.1038/sj.bjp.0705047