Synergistic effect of cholecystokinin octapeptide and angiotensin II in reversal of morphine induced analgesia in rats.
The aim of this paper is to study the synergistic anti-analgesic effect of angiotensin II (Ang II) plus cholecystokinin octapeptide (CCK-8). Our previous studies have shown that both CCK-8 and Ang II are potent anti-opioid substances. Intracerebroventricular (i.c.v.) injection of CCK-8 or Ang II dose-dependently antagonizes morphine-induced analgesia (MIA). In the present study, we observed the combined effect of CCK-8 and Ang II in antagonizing MIA. CCK-8 and Ang II were injected intracerebroventricularly to rats in various proportions and doses. The results were analyzed with isobolographic analysis. Combined injection of CCK-8 and Ang II in a ratio of 1 ng: 2.5 microg or 1 ng: 5 microg produced significantly greater effect in antagonizing MIA. The ED(50) of the two ratios are only 18.5% and 27.5%, respectively, of the theoretical dose of simple addition. We conclude that CCK-8 and Ang II used in such dose ratios may antagonize MIA synergistically.
Han
Nian-Lin
NL
Neuroscience Research Institute, Beijing Medical University, Beijing 100083, PR China Department of Physiology, Yian-Bei Nursing School, Datong, Shanxi, PR China.
Luo
Fei
F
Bian
Zhu-Ping
ZP
Han
Ji-Sheng
JS
D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors*; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012844:Sincalide / Q000008:administration & dosage / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
D000701:Analgesics, Opioid; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009020:Morphine; D012844:Sincalide