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)

125I-Bolton-Hunter sulfated cholecystokinin-8 was used to localize and characterize cholecystokinin (CCK) receptor binding sites in trigeminal and dorsal root ganglia, and in the spinal cord of the rat, rabbit, and monkey. In the rabbit and monkey, a substantial number, 90 +/- 21% and 24 +/- 8%, respectively, of trigeminal and dorsal root ganglion neurons express CCK binding sites. In the spinal cord, the highest concentration of CCK receptors is found in laminae I and II, which is the major termination site of dorsal root ganglia neurons expressing CCK receptor binding sites. Neonatal capsaicin treatment of the rat results in a 70% decline in CCK receptor binding sites in laminae I and II of the spinal cord, indicating that dorsal root ganglia neurons are a major source of CCK receptors in the spinal cord. Pharmacological experiments using selective CCK-A and CCK-B receptor antagonists demonstrate that CCK-B is the prominent CCK receptor subtype in trigeminal and dorsal root ganglia neurons in the rat, rabbit, and monkey. In the rat and rabbit spinal cord, CCK-B binding sites are the prominent subtype, whereas in the monkey cord, CCK-A is the prominent receptor subtype. These results demonstrate that CCK-B receptors are expressed by a substantial percentage of dorsal root ganglion neurons at all spinal levels, and that CCK may antagonize opiate analgesia at the level of the primary afferent neuron itself.
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PMID:Trigeminal and dorsal root ganglion neurons express CCK receptor binding sites in the rat, rabbit, and monkey: possible site of opiate-CCK analgesic interactions. 133 5

The effect of cholecystokinin octapeptide (CCK-8) and its analogue, ceruletide on release of acetylcholine (ACh) from the cerebral cortex was investigated in urethane-anaesthetized and in unanaesthetized rats. Cholecystokinin octapeptide and ceruletide markedly stimulated output of ACh at doses of 1.5 and 5.0 micrograms/kg (i.p.), respectively. This effect was prevented by proglumide (160 mg/kg i.p.), a specific cholecystokinin receptor antagonist. At doses of 10 micrograms/kg (i.p.) and more, both CCK-8 and ceruletide decreased output of ACh from the cerebral cortex. The decrease was prevented by naloxone (1 mg/kg, s.c.), and replaced by a short-lasting increase. Cholecystokinin octapeptide and ceruletide appear therefore to affect the activity of cortical cholinergic fibres by acting upon both specific and opiate receptors. The interaction between CCK-8 and ceruletide, and opiate receptors either direct or through the release of endogenous opiates, was also demonstrated by the antagonism between ceruletide (1, 5 and 10 micrograms/kg, i.p.) and analgesia induced by morphine (5 mg/kg, s.c.), evaluated by the tail-flick test in the rat.
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PMID:Effect of cholecystokinin octapeptide and ceruletide on release of acetylcholine from cerebral cortex of the rat in vivo. 609 46

The cholecystokinin (CCK) and gastrin families of peptides act as hormones and neuropeptides on central and peripheral CCK receptors to mediate secretion and motility in the gastrointestinal (GI) tract in the physiological response to a normal meal. CCK and its receptors are also widely distributed in the central nervous system (CNS) and contribute to the regulation of satiety, anxiety, analgesia, and dopamine-mediated behavior. Although the wide distribution, myriad number of functions, and reported pharmacological heterogeneity of CCK receptors would suggest a large number of receptor subtypes, the application of modern molecular biological techniques has identified two CCK receptors, CCK-A receptor (CCK-AR) and CCK-B receptor (CCK-BR), that mediate the actions of CCK and gastrin; gastrin receptors have been found to be identical to CCK-BR. CCK-AR, found predominantly in the GI system and select areas of the CNS, have high affinity for CCK and the nonpeptide antagonist L-364,718, whereas CCK-BR, found predominantly in the CNS and select areas of the GI system, have high affinity for CCK and gastrin and the nonpeptide antagonist L-365,260. Both CCK-AR and CCK-BR are highly conserved between species, although there is some tissue-specific variation in expression. Recombinant receptor expression faithfully reproduces the native receptor pharmacology and signal transduction pathways, allowing direct comparisons of receptor function between species as well as serving as a convenient source of receptor. Our present knowledge of the chromosomal localization, receptor gene structure, and primary sequence will allow further studies in disease association, receptor regulation, and structure-function analysis.
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PMID:Cholecystokinin receptors. 749 53

The predominant brain cholecystokinin receptor (CCK-B/gastrin) has been implicated in mediating many of the central effects of cholecystokinin, including anxiety, panic attacks, satiety, and analgesia, suggesting it is an important pharmacologic target. We now report the cloning and characterization of the cDNA encoding the human brain CCK-B/gastrin receptor. The cDNA was isolated from a human brain library by low stringency screening using the canine "gastrin" receptor cDNA as a hybridization probe. Nucleotide sequence analysis revealed an open reading frame encoding a 447-amino-acid protein with seven putative hydrophobic transmembrane domains and significant homology with other known members of the gastrin/cholecystokinin receptor family. Agonist and antagonist affinities of the recombinant human brain receptor expressed in COS-7 cells are consistent with a classical "CCK-B" receptor as defined by the literature. In COS-7 cells expressing the cloned receptor, CCK-8-stimulated phosphatidylinositol hydrolysis and intracellular Ca2+ mobilization suggesting second messenger signaling through phospholipase C. CCK-B/gastrin receptor transcripts were identified in human brain, stomach, and pancreas using high stringency Northern blot analysis. Southern blot hybridization analysis of human genomic DNA indicates that a single gene encodes both the brain and the stomach CCK-B/gastrin receptors. Our data suggest that the CCK-B and gastrin receptors are identical and that the long standing distinction between them may no longer apply.
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PMID:The human brain cholecystokinin-B/gastrin receptor. Cloning and characterization. 768 36

The analgesic effect of systemic morphine (4 mg/kg, s.c.) was antagonized in a dose-dependent manner by cholecystokinin octapeptide (CCK-8) (0.1-0.5 ng) administered bilaterally to the nucleus accumbens of the rat. This effect of CCK-8 could be reversed by devazepide, a CCK-A receptor antagonist, at 50 ng and 200 ng and by L-365,260, a CCK-B receptor antagonist, at 5 ng administered bilaterally to the nucleus accumbens. A marked potentiation of morphine analgesia was achieved by intra-nucleus accumbens injection of 200 ng devazepide or 5 ng L-365,260. Since the effect of L-365,260 in antagonizing the anti-opioid effect of CCK-8 in the nucleus accumbens is 40 times more potent than devazepide, it is suggested that the anti-opioid effect of CCK-8 is mediated by CCK-B receptors. In conclusion, nucleus accumbens is a strategic site where CCK-8 exerts an anti-opioid activity, most probably via the CCK-B receptors.
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PMID:Cholecystokinin octapeptide (CCK-8) antagonizes morphine analgesia in nucleus accumbens of the rat via the CCK-B receptor. 782 Jun 14

Primary treatment of patients suffering from acute pancreatitis is conservative, irrespective of its etiology and initial severity. There is no effective specific therapy for treating the underlying disease process. As a result, the current therapeutic approach involves the provision of supportive care, the elimination of causal (biliary tract) disease, and the treatment of complications. Since complications may develop at any time, patients with moderate or severe disease should be admitted to an intensive care unit for interdisciplinary assessment and constant observation of their clinical status and computed tomography findings. Basic therapy should include total fasting, replacement of deficits in volume, electrolyte and albumin, as well as adequate analgesia. Depending on the patient's specific clinical condition, nasogastric suction, respiratory support, antibiotics, insulin and heparin may become necessary. The use of enzyme inhibitors and drugs capable of inhibiting pancreatic exocrine secretion has not proved effective in clinical trials. The value of prostaglandins, non-steroidal anti-inflammatory drugs and cholecystokinin receptor antagonists remains to be established. Early endoscopic retrograde cholangiopancreatography should be performed in patients with suspected underlying biliary disease. Papillotomy should be carried out only when calculi are present in the common bile duct. Local complications, such as pseudocysts and abscesses can often be treated by ultrasound- or CT-guided aspiration and drainage. However, when bacterial infection of pancreatic necrosis becomes evident, surgical intervention should be considered. Future evaluation of new therapeutic approaches by controlled studies needs to include a sufficient number of patients with severe acute pancreatitis.
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PMID:Current conservative treatment of acute pancreatitis: evidence from animal and human studies. 811 38

CCK-8 administered bilaterally to the amygdala at 0.1-1.0 ng dose-dependently antagonized the analgesia induced by morphine (4 mg/kg, s. c.) as measured by the changes in tail flick latency (TFL). This effect of CCK-8 could be reversed by Devazepide, a CCK-A receptor antagonist dose-dependently at 50 ng and 200 ng, and by L-365, 260, a CCK-B receptor antagonist at 5 ng and 8 ng administered to the same site. The effect of morphine analgesia was potentiated by 200 ng Devazepide or 8 ng L-365, 260 administered bilaterally to amygdala. Devazepide and L-365, 260 per second showed no significant influence on basal TFL. The results indicate that amygdala is a strategic site where CCK-8 exerts an antiopioid activity. Since the effect of L-365, 260 was 25 times more potent than Devazepide, it suggests that the anti-opiod effect of CCK in amygdala is mediated by CCK-B receptors.
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PMID:[Cholecystokinin octapeptide (CCK-8) antagonizes morphine analgesia in amygdala of the rat]. 814 70

Cholecystokinin octapeptide (CCK-8) has been shown to be a neuropeptide with potent anti-opioid activity. Previous studies have shown that central administration of nanogram dose of CCK-8 totally abolished morphine analgesia in the rat, an effect mediated by CCK-B receptor in central nervous system. In the present study CCK-B antagonist L-365,260 was injected intracerebroventricularly (icv) to Wistar rats to see its effect on the analgesic effect induced by electroacupuncture (EA) stimulation. A marked potentiation of EA-induced analgesia was observed. The degree of potentiation depends on the frequency of EA used, with a rank order of 100 Hz > 15 Hz = 2/15 Hz > > 2 Hz. In a strain of rat with acoustically evoked epileptic seizure (P77PMC rats), an extra-ordinarily strong analgesic effect was produced in response to 100 Hz EA stimulation, which was similar to that in Wistar rats pre-treated with L-365,260. However, L-365,260 was not effective in potentiating EA analgesia in P77PMC rats. The results suggest that (1) high frequency EA is more likely to increase the release of CCK-8 in CNS as compared to low frequency EA, and (2) P77PMC rats may have a functional defect of the central CCK neurons in the nature of either a low CCK content or a reduced rate of release of CCK-8 in the CNS.
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PMID:CCK receptor antagonist L-365,260 potentiated electroacupuncture analgesia in Wistar rats but not in audiogenic epileptic rats. 819 76

Cholecystokinin octapeptide (CCK-8) in CNS has been shown to function as a neuropeptide with potent anti-opioid activity. It hinders opioid analgesia and facilitates opioid tolerance. The present study showed that electroacupuncture (EA) stimulation produced a marked increase of the CCK-8 immunoreactivity (ir) in the perfusate of the rat spinal cord. The increase of CCK-8-ir was most marked in response to EA of 100 Hz and 15 Hz, and less marked in response to EA of 2 Hz. Since CCK-8 has been shown to possess potent anti-opioid activity at the spinal level, blockade of the spinal CCK effect would be expected to potentiate EA-induced analgesia which is known to be opioid-mediated. Intrathecal (i.t.) administration of CCK-B antagonist L-365,260 per se did not affect tail flick latency (TFL) to any significant extent, yet it potentiated EA induced analgesia in a dose- and frequency-dependent manner. The potentiation was most marked at a dose range of 2.5-5.0 ng (i.t.) and at a frequency rank order of 100 Hz > 15 Hz > 2 Hz. The results suggest that an increased release of CCK-8 following EA may limit the effect of opioid peptides, and that the CCK-B receptor mediates the anti-opioid effect of CCK-8 in rat spinal cord.
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PMID:Increased release of immunoreactive CCK-8 by electroacupuncture and enhancement of electroacupuncture analgesia by CCK-B antagonist in rat spinal cord. 847 32

Extracellular single unit recordings were made from spinal dorsal horn wide dynamic range neurons in spinal transected, urethane-anesthetized rats. The unit discharges elicited by noxious electrical stimulation of the hind paw were suppressed by electroacupuncture (15 Hz, 0.3 ms, 3 mA, 30 min) placed at the hind leg points (S-36 and SP-6). Local spinal superfusion with naloxone (20 micrograms/15 microliters) or CCK-8 (10 ng/15 microliters) attenuated, whereas CCK-B receptor antagonist L365,260 (2.5 micrograms/15 microliters) enhanced the electroacupuncture effect. These findings provide further evidence for the notion that CCK-8, in the spinal cord, functions as an antiopioid substrate that antagonizes opioid- or electroacupuncture-induced analgesia.
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PMID:Cholecystokinin octapeptide reverses the inhibitory effect induced by electroacupuncture on C-fiber evoked discharges. 888 94


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