Involvement of different subtypes of cholecystokinin receptors in opioid antinociception in the mouse.
Various doses of sulfated cholecystokinin octapeptide (CCK-8s) injected intracerebroventricularly (ICV) alone did not show any antinociceptive effect. CCK-8s (0.01-1 ng) pretreated ICV for 10 min dose-dependently attenuated the inhibition of the tail flick response induced by ICV-administered morphine (2 micrograms). beta-endorphin (1 microgram), and U50,488H (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]benzeocetamide), 60 micrograms). However, ICV pretreatment with CCK-8s was not effective in reducing the inhibition of the tail flick response induced by [D-Pen(2)-D-Pen5]enkephalin (DPDPE; 10 micrograms) administered ICV. To determine what subtype(s) of CCK receptors are involved in antagonizing the antinociception induced by these opioids, effect of lorglumide sodium salt (a CCKA receptor antagonist) or PD135,158 N-methyl-D-glucamine salt (a CCKB receptor antagonist) on opioid-induced inhibition of the tail flick response was examined. Various doses of lorglumide sodium salt (lorglumide) or PD135,158 N-methyl-D-glucamine salt (PD135,158) injected ICV alone did not affect the basal tail flick response. The antagonistic effect of CCK-8s on morphine-, beta-endorphin-, and U50,488H-induced inhibition of the tail flick response was blocked in a dose-dependent manner by the co-ICV injection of PD135,158 (0.001-0.1 ng). The co-ICV injection of lorglumide (0.001-0.1 ng) dose-dependently blocked the antagonistic effect of CCK-8s on beta-endorphin- and U50,488H-induced, but not morphine-induced, inhibition of the tail flick response. Our results suggest that both CCKA and CCKB receptors are involved in antagonizing antinociception induced by beta-endorphin and U50,488H administered supraspinally. However, only CCKB (but not CCKA) receptors are involved in antagonizing antinociception induced by morphine administered supraspinally. CCK receptors are not involved in antagonizing the supraspinally administered DPDPE-induced antinociception.
Department of Pharmacology, College of Medicine, Hallym University, Chunchon, Kangwon-Do, South Korea.
H W
HW
Suh
Y H
YH
Kim
Y S
YS
Choi
D K
DK
Song
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000698:Analgesia; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D010147:Pain Measurement; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology; D001615:beta-Endorphin / Q000494:pharmacology
C090019:8-sulfocholecystokinin octapeptide; D000700:Analgesics; D004745:Enkephalins; D007211:Indoles; D009294:Narcotics; D011759:Pyrrolidines; D011949:Receptors, Cholecystokinin; C065600:PD 135158; D001615:beta-Endorphin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D008536:Meglumine; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; D011377:Proglumide; C048181:lorglumide; D012844:Sincalide