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Potentiation of [Met]enkephalin-induced antinociception by mixture of three peptidase inhibitors in rat.
- Source :
-
Journal of Anesthesia . Oct2014, Vol. 28 Issue 5, p708-715. 8p. - Publication Year :
- 2014
-
Abstract
- Purpose: Previous in vitro studies have shown that degradation of opioid peptides during incubation with cerebral membrane preparations is almost completely prevented by a mixture of three peptidase inhibitors (PIs), namely, amastatin, captopril, and phosphoramidon. In the present in vivo study, we evaluate the effects of intrathecal administration of these PIs on antinociception by [Met]enkephalin (ME) or PIs themselves. Methods: Drugs were administered into the thoracolumbar level of the spinal cord in the intrathecal space in rat. Induction of antinociception was measured by the tail immersion assay, with 55 °C as the nociceptive stimulus. Effects of PIs on antinociception were evaluated by dose-response study (ME, 1-20 nmol; PIs, 1-20 nmol each), by comparison of differences among two combinations of PIs (amastatin and captopril; captopril and phosphoramidon; amastatin and phosphoramidon) and three PIs (amastatin, captopril, and phosphoramidon), and by using opioid receptor selective antagonists. Results: Intrathecal administration of ME with these three PIs or PIs alone significantly and dose dependently increased antinociception in a μ- and δ-opioid receptor antagonist-reversible manner; moreover, the degree of antinociception with a combination of any two of these was less than that with all three, indicating that any residual single peptidase could inactivate significant amounts of ME. Conclusion: The present data, together with those of earlier studies, clearly demonstrate that amastatin-, captopril-, and phosphoramidon-sensitive enzymes play an important role in inactivation of opioid peptides at the spinal level. [ABSTRACT FROM AUTHOR]
- Subjects :
- *PEPTIDES
*OPIOIDS
*PEPTIDASE
*PROTEOLYTIC enzymes
*ENZYMES
Subjects
Details
- Language :
- English
- ISSN :
- 09138668
- Volume :
- 28
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Journal of Anesthesia
- Publication Type :
- Academic Journal
- Accession number :
- 98836869
- Full Text :
- https://doi.org/10.1007/s00540-014-1819-5