Antagonism of morphine analgesia by CCK-8-S does not extend to all assays nor all opiate analgesics

Barbaz, B. S.; Hall, Nancy; Liebman, Jeffrey M.

doi:10.1016/0196-9781(88)90195-7

Cited by 27 publications

(8 citation statements)

References 21 publications

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“…The peptide CCK has been widely heralded as an endogenous modulator of the la-opiate receptor whilst appearing to have little effect on effects mediated by the other subtypes of opiate receptor (Faris et al, 1983;Barbaz et al, 1989;Magnuson et al, 1990). In this study we have used the CCKB receptor antagonist, L-365,260, to demonstrate that in normal animals, under these experimental conditions, endogenous levels of CCK in the cord are sufficient to attenuate the antinociceptive actions of intrathecal morphine.…”

Section: Discussionmentioning

confidence: 99%

“…One candidate for this role is the peptide cholecystokinin (CCK) which acts predominantly at CCKB receptors in the rat spinal cord (Hill & Woodruff, 1990). Although there are some anomalies in the results from studies using CCK and CCK receptor antagonists, there is good evidence that the peptide CCK selectively interferes with the action of p.but not 6or ic-agonists at the level of the spinal cord (Faris et al, 1983;Barbaz et al, 1989;Magnuson et al, 1990). As yet, there has been no attempt to assign a physiological role to CCK in inflammatory states.…”

Section: Introductionmentioning

confidence: 99%

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Cholecystokinin as a factor in the enhanced potency of spinal morphine following carrageenin inflammation

Stanfa

Dickenson

1993

British J Pharmacology

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1Cholecystokinin (CCK) has been shown to diminish opioid analgesia. Here we investigate whether changes in the physiological levels of spinal CCK are responsible for the enhanced potency of spinal morphine in animals following carrageenin inflammation, as compared with normal animals. 2 Single dorsal horn nociceptive neurones were recorded in intact halothane-anaesthetized rats in the presence and absence of carrageenin-induced inflammation and comparisons were made between the two groups of animals. Inflammation was induced by the injection of 100fil of 2% A-carrageenin into the hind paw. 3 The inhibitory effect of intrathecal morphine on the C-fibre-evoked responses of the neurones was enhanced in the carrageenin-treated animals such that the effects of 0.25 jig and 10 gig of morphine in normal animals were comparable to those of 0. 01 fig and 2.5 fig in the carrageenin animals. The effect of 0.2 mg kg-' of the CCKB antagonist, L-365,260, on the antinociceptive potency of intrathecal morphine was examined in both groups of animals. In normal animals, L-365,260 produced a significant enhancement in the effect of morphine indicating a tonic CCK modulation in these animals, but it had no effect on the inhibitions produced by either dose of morphine in the carrageenin animals. 4 The inhibition of the C-fibre-evoked response produced by intrathecal morphine in the presence of 1 ptg of CCK was examined in both groups of animals. CCK attenuated the effects of morphine only in animals with carrageenin inflammation, having no effect on the action of morphine in normal animals. 5 The effects of both CCK and L-365,260 were therefore dependent on the inflammatory state of the animal, with each drug being active in opposite situations. 6 We propose that in normal animals, morphine may produce a maximal stimulation of the release of CCK such that exogenous CCK is unable to reduce further the analgesic effects under these conditions. However, the differential effects of the agonist and antagonist in the normal and inflamed rats points to a role of CCK in the enhanced opiate actions. This enhancement of the potency of spinal morphine in inflammation is best explained by a reduction in spinal CCK release by morphine in this state.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cholecystokinin as a factor in the enhanced potency of spinal morphine following carrageenin inflammation

Stanfa

Dickenson

1993

British J Pharmacology

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“…Furthermore, Flood and Morley (1989) showed that meal-associated enhancement of memory retention is influenced by the release of CCK8. The antiopiate effect of CCK8 also shows a similar dose-response relationship (Barbaz et al, 1988). This and other examples of hormesis were emphasized in the Jim Flood Memorial Lecture Distinguished Lectureship in 2004.…”

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confidence: 91%

Peptides and Hormesis

Kastin

Pan

2008

Critical Reviews in Toxicology

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Biology is replete with examples of hormesis, the term introduced and developed by Calabrese. The corresponding concept in the field of peptide research has been characterized as the inverted U-shaped dose-response relationship. The articles by Calabrese in this issue summarize the notable progress occurring in the past three decades. In contrast to the skepticism encountered when we introduced this concept for peptides in the early 1970s, hormesis is now becoming recognized as characteristic of many actions of these small proteins. Calabrese is performing a considerable service by his strong advocacy and promotion of the concept to a more general readership. Hopefully, hormesis will be routinely considered in the design of research projects and the discovery of pharmaceutical agents.

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“…cortex, thalamus, periaqueductal grey, medullary nuclei) and spinal cord associated with the control of nocicpetive information. In behavioural studies, CCK has been shown to modulate noxious stimuli in a complex manner with higher 'pharmacological' doses producing a naloxone-reversible antinociception (Barbaz et al, 1989;Hill et al, 1987b) whilst lower, more 'physiological' doses reverse the antinociception produced by exogenous, mainly morphine and endogenous opioids (Faris et al, 1983;Barbaz et al, 1989; endogenous CCK in the spinal cord and, consequently, CCKB antagonists appear no longer effective at modulating the morphine responses (Stanfa & Dickenson, 1993).…”

Section: Introductionmentioning

confidence: 99%

Effect of CCK receptor antagonists on the antinociceptive, reinforcing and gut motility properties of morphine

Singh

Oles

Field

et al. 1996

British J Pharmacology

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1 The ability of a selective CCKA receptor antagonist PD 140548 and a selective CCKB receptor antagonist CI-988 (formerly PD 134308) to modulate the various in vivo properties of morphine was investigated in the rat. 2 PD 140548 dose-dependently (0.001 -1.0 mg kg-1, i.p.) antagonised the development of conditioned place preference to morphine (2.0 mg kg'-, s.c.). In contrast, CI-988 (0.01 -1.0 mg kg-', i.p.) did not affect this morphine-induced behaviour. Neither of the CCK receptor antagonists blocked or generalised to the morphine (3.0 mg kg-', i.p.) discriminative stimulus. 3 CI-988 (0.001-10.0 mg kg-', s.c.) at doses of 0.05 and 0.1 mg kg-' (s.c.), potentiated the antinociceptive action of a threshold dose of morphine (5.0 mg kg-', i.p.) in a radiant heat model of acute nociception, the rat tail flick test. Furthermore, at 0.01 mg kg-' it potentiated the antinociceptive action of morphine (3.0 mg kg-') during the acute phase of the rat paw formalin test. And at doses of 0.01 and 0.1 mg kg-' it also potentiated the antinociceptive action of morphine (1.0 mg kg-') during the tonic phase of the formalin test. However, in both models, higher doses of CI-988 were ineffective. In contrast, PD 140548 (0.001 -10 mg kg-', s.c.) was only active at a dose of 1.0 mg kg-1 (s.c.) and only in the tonic phase of the formalin test. Neither CI-988 nor PD 140548 possessed any intrinsic antinociceptive action in either of the tests. Chronic treatment with CI-988 (0.01 mg kg-', s.c.) prevented the development of tolerance to morphine antinociception (4 mg kg-', s.c.) following a 6 day period of twice daily injections of morphine escalating from 1 to 16 mg kg-' (i.p.). 4 Morphine dose-dependently (1-10 mg kg-', s.c.) reduced the distance travelled by a charcoal meal in the rat intestine. Neither PD 140548 (0.01 -1.0 mg kg-', i.p.) nor CI-988 (0.01 -1.0 mg kg-', i.p.) potentiated or suppressed this inhibitory action of morphine. 5 In conclusion, the results of the present study indicate that CCKA and CCKB receptors modulate different properties of morphine. Thus, whilst a selective CCKA receptor antagonist blocked the rewarding properties of morphine, a selective CCKB receptor antagonist potentiated the antinociceptive action. However, neither compound displayed a potential for modulating the influence of morphine on gastro-intestinal motility. It is suggested that these findings may have important implications for development of CCK receptor antagonists as analgesic adjuncts to the therapeutic use of morphine.

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Antagonism of morphine analgesia by CCK-8-S does not extend to all assays nor all opiate analgesics

Cited by 27 publications

References 21 publications

Cholecystokinin as a factor in the enhanced potency of spinal morphine following carrageenin inflammation

Cholecystokinin as a factor in the enhanced potency of spinal morphine following carrageenin inflammation

Peptides and Hormesis

Effect of CCK receptor antagonists on the antinociceptive, reinforcing and gut motility properties of morphine

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