Antinociceptive profile of sulfated CCK-8. Comparison with CCK-4, unsulfated CCK-8 and other neuropeptides.
The antinociceptive activity of sulfated cholecystokinin octapeptide (CCK-8-S) was characterized by comparison with two other endogenous forms, unsulfated CCK-8 (CCK-8-U) and the carboxyl tetrapeptide fragment (CCK-4) and two other peptides present in the gut and brain: bombesin and neurotensin. By the intracerebroventricular (i.c.v.) route, CCK-8-S was antinociceptive in the hot plate and phenylquinone-induced writhing assays, but CCK-8-U and CCK-4 were active only in the latter test. By systemic administration, CCK-8-S retained anti-writhing activity but CCK-8-U and CCK-4 did not. Therefore, CCK receptors in brain may be involved in the apparent antinociception produced by CCK-8-U and CCK-4. Bombesin produced potent antinociceptive activity, along with a distinct, head-scratching syndrome, in both the writhing and hot plate tests. Naloxone reversed bombesin-induced elevation of latencies of mouse jump but not the head-scratching syndrome, indicating that the analgesic effect in the hot plate test was independent of the scratching behaviour. Neurotensin, unlike CCK-8-S, elevated tail-flick latencies, and was more potent in the writhing than in the hot plate test. Several differences between CCK-8-S and opioid substances included the need for relatively large doses of naloxone to block the effects of CCK-8-S in the phenylquinone-induced writhing test and the lack of effect of CCK-8-S in the tail-flick test. Global sedation can account for some, but not all, of the effects of CCK-8-S.(ABSTRACT TRUNCATED AT 250 WORDS)
D000700:Analgesics; D000818:Animals; D016227:Benzoquinones; D001839:Bombesin / Q000494:pharmacology; D006358:Hot Temperature / Q000009:adverse effects; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology*; D009496:Neurotensin / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D011809:Quinones; D012844:Sincalide / Q000494:pharmacology*; D013758:Tetragastrin / Q000494:pharmacology
D000700:Analgesics; D016227:Benzoquinones; D009479:Neuropeptides; D011809:Quinones; D013758:Tetragastrin; C029322:phenylbenzoquinone; D009270:Naloxone; D009496:Neurotensin; D012844:Sincalide; D001839:Bombesin