Unsulfated CCK-8 not blocked by proglumide or CR 1409 in the mouse abdominal irritant-induced stretching assay: possible central site of action.
Previous studies have shown that unsulfated cholecystokinin octapeptide (CCK-8-U) shares with the sulfated octapeptide (CCK-8-S) and the carboxyl-terminal tetrapeptide (CCK-4) the ability to block abdominal irritant-induced stretching when administered intracerebroventricularly. The effects of CCK-8-U, however, are not naloxone-reversible and do not appear upon systemic administration. To assess the hypothesis that the antistretching effects of CCK-8-U are mediated by central-type (CCK-B), rather than peripheral-type (CCK-A) receptors, the present experiments examined the reversal of these effects by CR 1409, a CCK receptor antagonist with in vitro selectivity for CCK-A receptors, and by proglumide. Both antagonists, when administered ICV, blocked the antistretching effects of CCK-8-S and CCK-4 (ICV), but not those of CCK-8-U. CR 1409 was approximately 40 times more potent against CCK-8-S by the ICV route than subcutaneously, indicating a likely action on CCK-A receptors in the brain. The effects of morphine, bombesin and neurotensin (ICV) were not blocked by CR 1409, indicating specificity for CCK receptor-mediated effects. The antistretching effects of CCK-8-U do not appear to be mediated by CCK-A receptors, and the possibility of a CCK-B receptor site of action must be considered.
Ambrose
F G
FG
Research Department, CIBA-GEIGY Corporation, Summit, NJ 07901.
Barbaz
B S
BS
Autry
W L
WL
Browne
R G
RG
Liebman
J M
JM
D000005:Abdomen; D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D005973:Glutamine / Q000031:analogs & derivatives*; D007509:Irritants; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology; D009496:Neurotensin / Q000494:pharmacology; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012026:Reflex, Stretch / Q000187:drug effects*; D012844:Sincalide / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D007509:Irritants; D005973:Glutamine; D009496:Neurotensin; D009020:Morphine; D011377:Proglumide; C048181:lorglumide; D012844:Sincalide; D001839:Bombesin