Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

New analogues of cholecystokinin-7 (CCK-7) modified at amino acid residues 5 and 7 were assayed for their effect on gall bladder, pancreatic secretion, food intake (anorectic activity), amount of rearing (sedative activity) and analgesia, as well as their ability to inhibit 125I-CCK-8 binding to pancreatic cell membrane receptors and brain membrane receptors. The results were compared to the activities of standard compounds, CCK-8, cerulein, BOC-CCK-7 (BOC = tertbutyloxycarbonyl) and BOC-[Nle2,Nle5]CCK-7. All analogues exhibited agonistic effects. Their anorectic activity was significantly prolonged.
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PMID:Pharmacological characterization of new cholecystokinin analogues. 128 May 92

Results from behavioural studies have shown that central cholecystokinin octapeptide (CCK-8) is a powerful antagonist against opioid effects and that an increased release of central CCK-8 plays an important role in the mechanisms of tolerance to morphine analgesia. No information is available concerning the rate of biosynthesis of CCK-8 in response to chronic morphine administration. Blot hybridization experiments made in the present study revealed a marked increase in preproCCK mRNA in the brain of rats receiving chronic morphine treatment for 1, 3 and 6 days, showing an increment of 52% (p < 0.05), 62% (p < 0.05) and 97% (p < 0.01) respectively. The results suggest that an acceleration of the expression of the CCK gene during long-term morphine treatment might constitute one of the mechanisms for morphine tolerance.
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PMID:Accelerated expression of cholecystokinin gene in the brain of rats rendered tolerant to morphine. 128 33

The effect of oxytocin (OT) and cholecystokinin octapeptide (CCK-8) on EA analgesia was studied in rats. The increase of 20.8-39.8% and 9.0-45.0% in pain threshold was observed respectively when ICV of CCK-8 or naloxone was combined with EA, these increases were lower than that in saline-EA group significantly, while the simultaneous ICV of OT and CCK-8 or OT and naloxone in combination with EA produced the increase of 76.2-116.6% and 41.8-104.5% in pain threshold separately. These results showed that only a small part in the role of OT enhancing EA analgesia was blocked by CCK-8 and naloxone. The data suggest that the role of OT in EA was not entirely dependent upon the endogenous opiate peptides.
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PMID:[Effect of oxytocin and cholecystokinin octapeptide (CCK-8) on electroacupuncture (EA) analgesia]. 128 28

1. The effect of chronic treatment with CI988, a recently developed selective antagonist of cholecystokinin type-B receptors (CCKB receptors) on the tolerance to morphine analgesia was studied in rats with the hot plate test. 2. Morphine tolerance was induced with the use of two paradigms. Morphine was injected i.p. either in a schedule of increasing doses (1-32 mg kg-1) twice daily for 6 days or at a fixed dose (3 mg kg-1) daily for 29 days. 3. In both series of experiments, tolerance to the analgesic effect of morphine was prevented by simultaneous treatment with i.p. CI988. Chronic treatment with only CI988 daily for up to 29 days did not reduce the analgesic effect of a weekly injection of morphine. 4. CI988 did not diminish the physical dependence to morphine, as examined with naloxone precipitated withdrawal. 5. The present results provide evidence that chronic treatment with a selective CCKB receptor antagonist could prevent tolerance to the analgesic effect of morphine without affecting morphine-induced physical dependence. Application of CCK antagonists may be clinically important in treating chronic pain patients by preventing morphine tolerance and by eliminating the need to increase morphine doses to unacceptable levels.
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PMID:CI988, a selective antagonist of cholecystokininB receptors, prevents morphine tolerance in the rat. 162 46

Intrathecal (ith) injection of cholecystokinin octapeptide (CCK-8) to the rat with single dose of 4 or 40 ng, or successive doses from 0.1 to 1 microgram at 10 min intervals produced neither analgesia nor hyperalgesia. However, the analgesia produced by ith injection of PL017, a specific mu-receptor agonist or 66A-078, a specific kappa-receptor agonist could be markedly antagonized by CCK-8 at a dose as small as 4 ng. In contrast, analgesia produced by ith injection of delta-agonist DPDPE could not be blocked by CCK-8 even at a dose as high as 40 ng. Since the effect of CCK-8 could be totally reversed by the CCK receptor antagonist proglumide, this effect is most probably mediated by CCK receptors.
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PMID:Cholecystokinin octapeptide antagonized opioid analgesia mediated by mu- and kappa- but not delta-receptors in the spinal cord of the rat. 197 19

CCK-8 has been shown to antagonize the analgesia produced by morphine or endogenous opioid peptides. The present study was performed to clarify the interaction between CCK-8 and different opioid ligands. Analgesia produced by intrathecal (I.T.) injection of the specific mu receptor agonist PL017 10 ng or kappa receptor agonist NDAP 500 ng can be antagonized by I.T. injection CCK-8 at a dose as small as 4 ng. In contrast, analgesia produced by I.T. injection of the delta receptor agonist DPDPE (6.5, 13 and 26 micrograms) was not blocked by CCK-8 (4 ng or 40 ng, I.T.). The antagonistic effect of CCK-8 on PL017 and NDAP could be completely reversed by proglumide (3 micrograms, I.T.). I.T. injection of CCK-8 (4 or 40 ng single dose or cumulative dose of 0.1, 0.2, 0.5 and 1.0 microgram at 10 min intervals) produced neither analgesia nor hyperalgesia. In conclusion, CCK-8 preferentially antagonizes opioid analgesia mediated by mu and kappa receptors, and this antagonistic effect is mediated by CCK receptors.
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PMID:[Cholecystokinin octapeptide (CCK-8) antagonized analgesia mediated by mu and kappa opioid receptors]. 198 23

Cholecystokinin octapeptide (CCK-8) and angiotensin I (AI) have been shown in behavioral studies being endogenous antiopioid substrates (AOS). To assess their antiopioid mechanism at postreceptor level, we observed the effects of the three opioids and the two AOS on 45Ca uptake of the rat spinal synaptosomal preparations. Morphine, Dyn A and DPDPE at concentrations of 10 nmol/L to 1 mumol/L, produced a mild suppression of 45Ca uptake of synaptosomal preparations from ventral spinal cord. CCK-8 showed a mild suppression only at a concentration of 1 mumol/L. In synaptosomes prepared from dorsal spinal cord, Dyn A but not morphine or DPDPE, produced a strong inhibition of 45Ca uptake which was blocked by nor-BNI, a kappa receptor antagonist, at 1 mumol/L. While CCK-8 (10 nmol/L to 1 mumol/L) also suppressed 45Ca uptake, it could antagonize the suppressive effect induced by Dyn A. In contrast to CCK-8, AI (10 nmol/L to 1 mumol/L) influenced neither on synaptosomal 45Ca uptake, nor on Dyn A suppression of 45Ca uptake. The results presented above fit very well with our behavioral studies, i.e., CCK-8 antagonized opioid analgesia in both the brain and the spinal cord, whereas AI antagonized opioid analgesia in the brain but not in the spinal cord. It is therefore concluded that antagonism of the opioid suppression of synaptosomal 45Ca uptake might be one of the mechanisms for the antiopioid activity of CCK-8 and AI.
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PMID:[Effects of dynorphin A and CCK-8 on synaptosomal 45Ca uptake of the rat spinal cord]. 198 24

Extracellular single unit recordings were made from dorsal horn nociceptive neurons of intact, urethane-anesthetized rats during controlled electrical stimulation of the hind paw. Neither local superfusion of cholecystokinin octapeptide (CCK; 6.4 pmol to 20 nmol) nor the CCK antagonist lorglumide (LGM; 145 fmol to 145 pmol) significantly altered A- or C-fiber evoked firing or spontaneous activity. Pretreatment with CCK, however, significantly attenuated, whereas LGM enhanced, morphine-induced inhibition of C-evoked firing. These findings provide further evidence that CCK functions as a selective antagonist of opioid-induced analgesia.
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PMID:Cholecystokinin and its antagonist lorglumide respectively attenuate and facilitate morphine-induced inhibition of C-fiber evoked discharges of dorsal horn nociceptive neurons. 205 23

Cholecystokinin-octapeptide (CCK-8) has been shown to antagonize the analgesia produced by opioid peptides. The present study was performed to evaluate its effect on cardiovascular regulatory functions of opioids. Both CCK-8 and opioid peptides were injected intrathecally (ith) in pentobarbital anaesthetized rats. The depressive effects induced by the mu agonist PL017 (5 micrograms), delta agonist DADLE (25 micrograms) and kappa agonist 66A-078 (1 microgram) were antagonized by CCK-8 within a dosage of 10 micrograms in a dose dependent manner. CCK-8 can also partly antagonize the bradycardiac effects induced by PL017, DADLE and 66A-078. The antagonistic effect of CCK-8 on DADLE in MAP could be reversed by pretreatment with CCK receptor antagonist proglumide (100 micrograms). No significant changes in MAP were found following ith administration of CCK-8 0.5-10 micrograms and proglumide 100 micrograms, but a large dose (50 micrograms) of CCK-8 lowered MAP dramatically. The results suggest that within a certain range of dose CCK-8 in spinal cord may play an antagonistic role against opioid effects in the regulation of cardiovascular function and this effect of CCK-8 seems to be mediated by CCK receptor. These results support the hypothesis that CCK-8 may act as an anti-opioid substance in the CNS of the rat.
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PMID:[Cholecystokinin-octapeptide antagonizes the central depressive effect of opioid peptides in rats]. 206 85

It has been reported that proglumide and L-364,718 potentiate opioid-induced antinociception. However, their mode of action in pain modulation is still not understood. To evaluate a possible interaction with opioid receptors, we determined the affinities of the CCK antagonists proglumide, lorglumide, benzotript and L-364,718 on mu, delta and kappa binding sites, using guinea pig brain crude synaptosome preparations. These affinities were compared to that of the central CCK binding site, using rat brain slide-mounted sections. At 100 microM, proglumide competed for 13% and 17% of mu and kappa binding sites, but did not interact with delta and CCK sites. At this concentration, lorglumide reduced mu, delta, kappa and CCK specific binding by 44%, 69%, 35% and 88%, whereas benzotript diminished it by 16%, 13%, 38% and 48%, respectively. L-364,718 did not interact with opioid receptors (assay limit of solubility, 10 microM) but had a high affinity for CCK binding sites (IC50, 126nM). The lack of selectivity of proglumide, lorglumide and benzotript for CCK receptors suggests that their reported ability to potentiate morphine analgesia may be related to an interaction with opioid receptors.
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PMID:Cholecystokinin antagonists proglumide, lorglumide and benzotript, but not L-364,718, interact with brain opioid binding sites. 217 22


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