Jpn J Pharmacol. 1994 Nov; 66(3): 337-45.

Effects of a mixture of peptidase inhibitors (amastatin, captopril and phosphoramidon) on Met-enkephalin-, beta-endorphin-, dynorphin-(1-13)- and electroacupuncture-induced antinociception in rats.

Kishioka S, Miyamoto Y, Fukunaga Y, Nishida S, Yamamoto H.

Department of Pharmacology, Wakayama Medical College, Japan.

The effects of a mixture of three peptidase inhibitors (PIs), amastatin, captopril and phosphoramidon, on methionine-enkephalin (Met-enk)-, beta-endorphin (beta-end)-, dynorphin-(1-13) (Dyn)- and electroacupuncture (EA)-induced antinociception were compared in rats. EA was performed by passing electric pulses (3 Hz, 0.1-msec duration, for 45 min) through acupuncture needles inserted into the Hoku-point. The antinociceptive effect was estimated by the hind paw pressure test. The antinociceptive effects of Met-enk and beta-end injected i.c.v. or i.t. and of Dyn injected i.t. were clearly potentiated by the PIs pretreated by the same administration routes as used for the injection of opioid peptides. The antinociceptive effects of Met-enk, beta-end and Dyn injected i.c.v. were also potentiated significantly by i.t.-PIs. PIs injected into the periaqueductal gray (PAG) potentiated EA antinociception. However, the EA effect was not affected by i.t.-PIs and was rather attenuated by i.c.v.-PIs. These results suggest that: i) Met-enk hydrolyzing enzymes are involved in the degradation of not only Met-enk but also beta-end and Dyn in the rat central nervous system; ii) Met-enk and beta-end act on both supraspinal and spinal sites, while Dyn acts only on the spinal site; iii) EA antinociception is mediated by supraspinal Met-enk and/or beta-end; and iv) an anti-opiate peptide system may be activated by EA stimulation, being susceptible to Met-enk hydrolyzing enzymes.