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)

The cannabinoid receptor that has been pharmacologically characterized for hypothermia, spontaneous activity, analgesia and catalepsy in rodents is the same pharmacological receptor that inhibits adenylate cyclase in vitro. The inhibition of adenylate cyclase by the cannabinoid receptor results from an interaction with Gi, based on the biochemical kinetic properties of the response, the sensitivity to pertussis toxin ADP-ribosylation, and the thermodynamic characteristics of the response. From precedents based on studies of the well-characterized G protein coupled receptors, rhodopsin and the beta-adrenergic receptor, we can predict the tertiary structure of the cannabinoid receptor. Three sites of potential glycosylation are present on the receptor. However, treatment of N18TG2 neuroblastoma cells with tunicamycin to prevent glycosylation of newly synthesized receptors failed to alter cannabinoid-induced inhibition of cyclic AMP accumulation. The cannabinoid response was rapidly desensitized (within 1/2 h). Treatment of cells with tunicamycin failed to alter agonist-induced desensitization processes. These findings can be more veraciously interpreted as we gain a better understanding of the cellular dynamics of the cannabinoid receptor.
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PMID:The cannabinoid receptor: biochemical and cellular properties in neuroblastoma cells. 180 46

Cholera toxin, an agent that impairs the function of Gs transducer proteins, was injected (0.5 microgram/mouse, icv) and the antinociceptive activity of opioids and clonidine was studied 24h later in the tail-flick test. In these animals, an enhancement of the analgesic potency of morphine, beta-endorphin and clonidine could be observed. Cholera toxin did not modify the antinociception evoked by the enkephalin derivatives DAGO and DADLE. Pertussis toxin that catalyses the ADP ribosylation of alpha subunits of Gi/Go regulatory proteins was given icv (0.5 microgram/mouse). This treatment reduced the analgesic effect of opioids and clonidine. However, while the analgesia elicited by DAGO, DADLE and clonidine was greatly decreased, the effect of morphine and beta-endorphin was reduced to a moderate extent. It is concluded that Gi/Go regulatory proteins functionally coupled to opioid and alpha 2 receptors are implicated in the efficacy displayed by opioids and clonidine to produce supraspinal analgesia. Moreover, these two receptors are susceptible to regulation by a process that might involve a Gs protein.
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PMID:Cholera toxin and pertussis toxin on opioid- and alpha 2-mediated supraspinal analgesia in mice. 185 Apr 93

Six days after intracerebroventricular pretreatment of rats with pertussis toxin (PTX 0.5 microgram/rat) there was a marked decrease in the antinociceptive effect of morphine, regardless of the route of opioid administration (into the periaqueductal gray matter, intrathecally or intraperitoneally) or the analgesic test used (tail flick and jaw opening reflex). PTX pretreatment also partially attenuated the naloxone-precipitated withdrawal syndrome in morphine-dependent rats, significantly reducing teeth chattering, rearing and grooming. These in vivo findings indicate that G-protein-dependent mechanisms are involved in morphine analgesia and dependence. The biochemical mechanism could be related to ADP ribosylation of Gi coupled to the adenylate cyclase system, but an interaction of PTX with other G-proteins linked to different second messengers or directly to ionic channels cannot be excluded.
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PMID:Pertussis toxin inhibits morphine analgesia and prevents opiate dependence. 231 51

The influence of bupivacaine and its major metabolite, pipecoloxylidide, on human platelet function was studied in vitro. Significant inhibition of ADP and collagen-induced platelet aggregation occurred only with concentrations of bupivacaine above 10 micrograms.ml-1. This concentration (10-25 micrograms.ml-1) is much higher than would be expected in routine clinical use of bupivacaine for epidural analgesia. The inhibition of platelet aggregation was associated with a significant decrease in beta-thromboglobulin secretion. In contrast, pipecoloxylidide had no effect on platelet aggregation or the beta-thromboglobulin release. We conclude that the previously reported 30-min time-lag between the maximal plasma concentration of bupivacaine and the inhibition of platelet aggregation is unlikely to be due to a metabolism of bupivacaine to pipecoloxylidide.
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PMID:The effects of bupivacaine and pipecoloxylidide on platelet function in vitro. 252 32

Ketorolac is a potent analgesic agent with antiplatelet properties which is known to cross the placenta. The aim of this study was to determine whether maternal administration of ketorolac in labour had any effect on neonatal platelet function as compared with maternal administration of pethidine and prochlorperazine. Eighteen parous women were studied in labour, twelve received pethidine (control) and six received ketorolac for analgesia. Immediately after delivery, blood was taken from the umbilical vein and anticoagulated with citrate. Platelet aggregation in whole blood was studied. Ketorolac significantly inhibited aggregation in response to arachidonic acid and collagen but not ADP. These findings confirm that ketorolac crosses the placenta. The antiplatelet effects are likely to be related to ketorolac's inhibitory effect on TxA2 production which is required for arachidonic acid and collagen-induced aggregation, but not the primary aggregation response induced by ADP. These effects suggest that ketorolac should be used with caution in patients whose neonates are at risk of haemostatic problems.
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PMID:Effect of maternal ketorolac administration of platelet function in the newborn. 326 21

31P NMR studies on the brains of living rabbits were carried out at 32 MHz in a spectrometer having a 200-mm clear bore. Paralyzed pump-ventilated animals under nitrous oxide analgesia were inserted into the 1.89-T field and signals were focused in the brain by using a 4-cm surface coil. Several conventional physiological variables were monitored together with 31P spectra during induction and reversal of insulin shock and hypoxic hypoxia sufficient to abolish the electroencephalogram and during status epilepticus. A reversible decrease in phosphocreatine stores accompanied by an increase in Pi was detected during hypoglycemia and hypoxia. Similar changes were observed in prolonged status epilepticus but were not reversed. ATP levels fell about 50% in hypoglycemia but only slightly in the other two metabolic stresses. Intracellular pH rose in hypoglycemia; in status epilepticus and hypoxia it fell, but only when cardiovascular function was severely impaired. From the measured NMR parameters and the assumptions (i) that creatine kinase was at equilibrium and (ii) that the creatine/phosphocreatine pool was constant, it was possible to calculate the relative changes in cytoplasmic ADP levels associated with these metabolic disturbances.
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PMID:Cerebral metabolic studies in vivo by 31P NMR. 657 78

In order to evaluate the impact of minor surgery on platelet aggregability and the effect of anaesthesia on this parameter, we allocated 14 otherwise healthy men for inguinal herniotomy to either general anaesthesia (n = 7) or lumbar epidural anaesthesia (n = 7). Platelet aggregation threshold to adenosine diphosphate (ADP-threshold) was measured before and after anaesthesia, prior to surgery, at the end of surgery and during the following hours as well as on the first post-operative morning. General anaesthesia did not affect ADP-threshold while epidural analgesia itself induced a significant increase. During and soon after surgery the ADP-threshold increased in those receiving general anaesthesia while in those receiving epidural analgesia the ADP-threshold returned to pre-operative levels. On the first post-operative morning both groups showed a significantly lower ADP-threshold as compared to the pre-operative level. Surgery induced an increase in 3'5' cyclic-adenosine monophosphate (cAMP). This adrenergic response was attenuated by epidural analgesia.
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PMID:General versus regional anaesthesia and platelet aggregation in minor surgery. 805 Apr 21

Pertussis toxin (PTX), which causes the ADP-ribosylation and thereby inactivation of Gi-proteins, has been employed in analgesia testing to elucidate receptors that are coupled to inhibitory G-proteins, such as the mu-opioid receptor. Consistent with previous findings, the antinociceptive effects of morphine (1-10 microg) as measured by tail-flick latency using a 55 degrees C water bath, were blocked by a single intrathecal injection of 0.5 microg PTX 6 days prior to intrathecal morphine administration. In addition, mice treated intrathecally with 0.5 microg of PTX had significantly shorter baseline tail-flick latencies compared with vehicle treated mice using a 55 degrees C water bath when tested 6 days after PTX or vehicle administration. Morphine-induced antinociception was blocked in a dose-dependent manner by PTX with complete blockade of morphine following a 0.3-microg dose of PTX. Further, mice administered 0.1 microg or 0.3 microg PTX intrathecally had significantly shorter tail-flick latencies compared with vehicle injected mice using a 40, 45 or 50 degrees C water bath when tested 7 days after intrathecal injection. Shorter tail-flick latencies were observed at 45 degrees C as early as 48 h after intrathecal administration of 0.03, 0.1 or 0.3 microg PTX and these shorter tail-flick latencies were observed up to 90 days after intrathecal PTX administration. The intrathecal administration of PTX caused hyperalgesia and allodynia that appears similar to the symptoms reported by patients suffering from neuropathic pain, and suggests that deficiencies in inhibitory systems, as compared with increases in excitatory systems, may play a role in the pathophysiology of at least some central or neuropathic pain states.
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PMID:Intrathecal pertussis toxin produces hyperalgesia and allodynia in mice. 915 Feb 97

Therapeutic options in acute coronary syndrome (unstable angina pectoris/non-Q-wave myocardial infarction), as also in acute Q-wave infarction, include conservative medical and mechanical-interventional measures. Early hospitalization for surveillance and induction of treatment is always necessary. Administration of oxygen, analgesia, sedation and treatment with nitrates, beta blockers or calcium antagonists, acetylsalicylic acid (ASA) and heparin are the basic measures. As alternatives to ASA, the new ADP antagonists, ticlopidine, clopidogrel, and as an alternative to heparin, hirudin or low-molecular-weight heparins can be used. If this does not result in rapid clinical stabilisation (here, transient ST-T changes in the ECG and the detection of troponine I or T represent major risk indicators) the new glycoprotein-IIb/IIIa receptor antagonists may be employed as highly potent platelet aggregation inhibitors. In addition, the patients should then undergo coronary angiography prior to interventional treatment of the underlying coronary stenosis.
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PMID:[Current therapeutic strategies in acute coronary syndrome. New and established drug and interventional therapy]. 1089 39

Adenosine produces analgesia in the spinal cord and can be formed extracellularly through enzymatic conversion of adenine nucleotides. A transverse push-pull microprobe was developed and characterized to sample extracellular adenosine concentrations of the dorsal horn of the rat spinal cord. Samples collected via this sampling technique reveal that AMP is converted to adenosine in the dorsal horn. This conversion is decreased by the ecto-5'-nucleotidase inhibitor, alpha,beta-methylene ADP. Related behavioral studies demonstrate that AMP administered directly to the spinal cord can reverse the secondary mechanical hyperalgesia characteristic of the intradermal capsaicin model of inflammatory pain. The specific adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT) inhibits the antihyperalgesia produced by AMP. This research introduces a novel microprobe that can be used as an adjunct sampling technique to microdialysis and push-pull cannulas. Furthermore, we conclude that AMP is converted to adenosine in the dorsal horn of the spinal cord by ecto-5'-nucleotidase and subsequently may be one source of adenosine, acting through adenosine A(1) receptors in the dorsal horn of the spinal cord, which produce antihyperalgesia.
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PMID:A novel transverse push-pull microprobe: in vitro characterization and in vivo demonstration of the enzymatic production of adenosine in the spinal cord dorsal horn. 1114 97


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