Opioid Control of the In Vitro Release of Cholecystokinin-Like Material from the Rat Substantia Nigra
Article first published online: 5 OCT 2006
Journal of Neurochemistry
Volume 58, Issue 3, pages 916–922, March 1992
How to Cite
Benoliel, J. J., Mauborgne, A., Bourgoin, S., Legrand, J. C., Hamon, M. and Cesselin, F. (1992), Opioid Control of the In Vitro Release of Cholecystokinin-Like Material from the Rat Substantia Nigra. Journal of Neurochemistry, 58: 916–922. doi: 10.1111/j.1471-4159.1992.tb09344.x
- Issue published online: 5 OCT 2006
- Article first published online: 5 OCT 2006
- Received January 3, 1991; revised manuscript received June 22, 1991; accepted July 30, 1991.
- evoked release;
- Substantia nigra;
- μ- and δ-opioid receptors;
- Peptidase inhibitors
Abstract: Possible interactions between Met-enkephalin and cholecystokinin (CCK)-containing neurons in the rat sub-stantia nigra were investigated by looking for the effects of various opioid receptor ligands and inhibitors of enkephalin-degrading enzymes on the K+-evoked overflow of CCK-like material (CCKLM) from substantia nigra slices. The δ-opioid agonists d-Pen2,dPen5-enkephalin (50 μM) and Tyr-D-Thr-Gly-Phe-Leu-Thr (DTLET; 3 μM) enhanced, whereas the n-opioid agonists Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGO; 10 μM) and MePhe3, D-Pro4-morphiceptin (PL 017; 10 μM) decreased, the K+-evoked release of CCKLM. By contrast, the δ-opioid agonist U-50488 H (5 μM) was inactive. The stimulatory effect of DTLET could be prevented by the 5 antagonist ICI-154129 (50 μM but not by the μ antagonist naloxone (1 μM). Conversely, the latter drug, but not ICI-154129, prevented the inhibitory effect of DAGO and PL 017. A significant increase in CCKLM overflow was observed upon tissue supervision with the peptidase inhibitors kelatorphan or bestatin plus thiorphan. This effect probably resulted from the stimulation of δ-opioid receptors by endogenous enkephalins protected from degradation, because it could be prevented by ICI-154129 (50 μM Furthermore, the peptidase inhibitors did not enhance CCKLM release further when S-opioid receptors were stimulated directly by DTLET (3 μM). These data indicate that opioids acting on d and n receptors may exert an opposite influence, i.e., excitatory and inhibitory, respectively, on CCK-containing neurons in the rat substantia nigra. Because CCK has anti-opioid properties, the δ-opioid control of CCKLM release might participate in the central mechanisms of opiate tolerance.