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 blood cyclic AMP level was determined just before, during and after induced labour in 27 healthy women. To achieve complete pain relief during the first stage of labour, 14 of them were given segmental epidural analgesia at the height of Th 10-12. The remaining parturients served as controls. Cyclic AMP was above the normal non-gravid level before induction in both groups. In the control group the cyclic AMP content decreased during the first stage of labour, then it increased and reached a peak at the moment of delivery. These changes were, however, not significant. In the epidural group the cyclic AMP level rose significantly during the first stage, and also reached its peak at the moment of delivery. There was a statistically significant difference between the groups at a cervical dilatation of 6-8 cm. After delivery the cyclic AMP rapidly declined to its initial value in both groups. The possible role of the decreased uterine contractions after the block in the increase of the cyclic AMP is discussed.
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PMID:Cyclic AMP and segmental epidural analgesia during labour. 19 31

Cyclic AMP, glucose and cortisol in plasma were measured in three groups of patients undergoing hysterectomy. The operations were performed under general anaesthesia, under general anaesthesia combined with epidural analgesia and under epidural analgesia alone. Surgery elicited a significant rise in plasma cyclic AMP, glucose and cortisol when performed under general anaesthesia alone. Epidural analgesia extending from T4-6 to S5 combined with general anaesthesia abolished the rise in cyclic AMP and reduced the increase in glucose and cortisol and epidural analgesia alone extending from T4 to S5 blocked the rise in glucose and cortisol as well as that in cyclic AMP. The results support the theory that afferent nerve impulses from the area of trauma are of major importance for the catabolic state induced by surgical procedures and indicate that anaesthetic management which includes blockade of afferent nerve impulses which includes blockade of afferent nerve impulses from the area of trauma can be reduce the catabolic response to surgery. These observations could be of value in the operative management of patients with diabetes mellitus and possibly in other groups by patients with a high surgical morbidity.
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PMID:Inhibition of plasma cyclic AMP, glucose and cortisol response to surgery by epidural analgesia. 20 31

Oral administration of an infusion of lemongrass (Cymbopogon citratus) fresh leaves to rats produced a dose-dependent analgesia for the hyperalgesia induced by subplantar injections of either carrageenin or prostaglandin E2, but did not affect that induced by dibutyryl cyclic AMP. These results indicate a peripheral site of action which was confirmed with the essential oil obtained by steam distillation of the leaves. Silica gel column fractionation of the essential oil allowed the identification of myrcene as the major analgesic component in the oil. Identification of the components was made by thin-layer chromatography and checked by mass spectrometry. The peripheral analgesic effect of myrcene was confirmed by testing a standard commercial preparation on the hyperalgesia induced by prostaglandin in the rat paw test and upon the contortions induced by intraperitoneal injections of iloprost in mice. In contrast to the central analgesic effect of morphine, myrcene did not cause tolerance on repeated injection in rats. This analgesic activity supports the use of lemongrass tea as a "sedative" in folk medicine. Terpenes such as myrcene may constitute a lead for the development of new peripheral analgesics with a profile of action different from that of the aspirin-like drugs.
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PMID:Myrcene mimics the peripheral analgesic activity of lemongrass tea. 175 86

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

Protein kinase C (PKC) has been shown to be an important substrate in intracellular signal transduction. Very little is known concerning its possible role in mediating opiate-induced analgesia. In the present study, 12-O-tetradecanoylphorbol 13-acetate (TPA), a selective activator of PKC, was injected intrathecally (ith) to assess its influence on the analgesia induced by intrathecal injection of the mu opioid agonist PL017, the delta agonist DPDPE and the kappa agonist 66A-078. Radiant heat-induced tail flick latency (TFL) was taken as an index of nociception. TPA in the dose of 25-50 ng, which did not affect the baseline TFL, produced a marked suppression of opioid antinociception, with a higher potency in blocking mu and delta than the kappa effect. In addition, mu and delta agonists induced remarkable decreases in spinal cyclic AMP (cAMP) content whereas the kappa effect was weak. The results suggest a cross-talk between the PKC system and the signal transduction pathway subserving opioid analgesia.
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PMID:Phorbol ester suppression of opioid analgesia in rats. 197 38

Multiple modulatory effects of opioids on the duration of the calcium component of the action potential (APD) of dorsal-root ganglion (DRG) neurons of mouse spinal cord-ganglion explants were studied. The APD of DRG neuron perikarya has been previously shown to be shortened by exposure to high concentrations of opioids (ca. 0.1-1 microM) in about 1/2 of the cells tested. The present study demonstrates that in addition to these inhibitory modulatory effects of opioids, lower concentrations (1-10 nM) of present study demonstrates that in addition to these inhibitory modulatory effects of opioids, lower concentration (1-10 nM) of delta- mu, and kappa-opioid agonists elicit excitatory modulatory effects, i.e. prolongation of the APD, in about 2/3 of the sensory neurons tested. APD prolongation as well as shortening elicited by delta, mu, and kappa agonists were prevented by coperfusion with the opioid antagonists, naloxone or diprenorphine (10 nM). APD prolongation induced by the delta-agonist [D-Ala2-D-Leu5]enkephalin (DADLE) was prevented in the presence of multiple K+ channel blockers, whereas excitatory modulation by the specific kappa-agonist, U-50,488H was not attenuated under these conditions. After treatment of DRG neurons with pertussis toxin (1 micrograms/ml for several days) or forskolin (50 muM for less than 15 min), a much smaller fraction of cells showed opioid-induced APD shortening; moreover, a much larger fraction of cells showed opioid-induced APD prolongation, even when tested with high concentrations of DADLE (1-10 muM). These data indicate that opioid-induced APD prolongation is not mediated by pertussis toxin-sensitive G proteins (which have been shown to regulate opioid inhibitory effects) and suggest that elevation of cyclic AMP levels may enhance opioid excitatory responsiveness. Furthermore, our analyses indicate that mu-, delta- and kappa-subtypes of excitatory as well as inhibitory opioid receptors may be expressed on the same DRG neuron perikaryon under in vitro conditions. If dual opioid modulation of the APD of DRG perikarya also occurs in central DRG terminals this may play a significant role both in nociceptive signal transmission as well as tolerance to opioid analgesia.
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PMID:Dual opioid modulation of the action potential duration of mouse dorsal root ganglion neurons in culture. 254 63

The study of clinical manifestations and cardiodynamics in macrofocal myocardial infarction was conducted a few hours or days since the disease onset. Altogether 36 patients were examined. Obsidan administration was employed in 24 patients, basic indication to its use being clinico-hemodynamic++ signs of sympathetic hyperactivity. Clinical response to the drug was correlated with reactions of neurohumoral adaptation of the acute phase: levels of cyclic AMP, GMP and serotonin. Potentiating effect on obsidan analgesia, resolution of clinical symptoms of sympathetic hypertonus efficient energetic regime of the heart are mediated by activation of stress-limiting systems, i.e. links of cGMP and serotonin mechanisms.
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PMID:[Mechanisms of the effect of obsidan on the clinical picture of myocardial infarction at the early stage of the disease]. 261 6

With several notable exceptions, interest in the area of multiple molecular forms of phosphodiesterase remained relatively dormant during the decade following Thompson's discovery of more than one phosphodiesterase in brain in 1971. Within the last several years, however, over 20 novel agents have been identified that exert selective inhibitory effects on the various molecular forms of phosphodiesterase present within different cells. In addition, several studies have documented that such agents can produce discrete changes in cyclic AMP and cyclic GMP, an action that is not shared by "first generation" phosphodiesterase inhibitors such as theophylline. The purpose of this Perspective is to provide some clarity to this rapidly evolving area of selective phosphodiesterase inhibitors. Thus, we have attempted to characterize the different forms of phosphodiesterase present in various tissues and cells according to their kinetic properties, substrate specificity, etc. and also to characterize those major classes of agents that have been shown to inhibit phosphodiesterase activity, whether selectively or nonselectively. In addition, we have described several therapeutic areas wherein selective phosphodiesterase inhibitors might prove efficacious, paying particular attention to those areas in which selective phosphodiesterase inhibitors have already been shown to exert beneficial effects, namely, stimulation of myocardial contractility, inhibition of mediator release, and inhibition of platelet aggregation. Although focusing on these three areas, it is obvious that the potential therapeutic utility of selective phosphodiesterase inhibitors could conceivably extend to several other areas in which modulation of cyclic nucleotides can have desirable effects, including cancer chemotherapy, analgesia, the treatment of depression, Parkinson's disease, and learning and memory disorders. For example, the selective type III phosphodiesterase inhibitor rolipram has been shown to antagonize reserpine-induced hypothermia and also to potentiate yohimbine lethality, two tests that are indicative of antidepressant activity. In addition, microinjection of the selective PDE III inhibitor Ro 20-1724 into the rat brain stem has been shown to produce analgesia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A new generation of phosphodiesterase inhibitors: multiple molecular forms of phosphodiesterase and the potential for drug selectivity. 298 81

Pharmacological interactions between morphine (Mor; analgesia), pentobarbital (Pent; hypnosis), ethanol (EtOH; rotarod adaptability), amphetamine (AMP; ambulation), and cocaine (Coca; ambulation) were examined in mice after a single or repeated administrations. Pretreatment with each drug, even a single dose, resulted in a modification of the effect of succeeding drugs. After 6-day daily treatment with drugs, tolerance developed to Mor, Pent, and EtOH, while reverse tolerance was developed to AMP and Coca. Development of tolerance to Pent was accelerated in the animals that were chronically treated with other drugs. Cross reverse-tolerance was obtained between AMP and Coca, on the other hand, one-way cross tolerance was observed between Mor and EtOH. A marked change was observed in the effect of each drug when administered at the peak time of withdrawal signs of Mor, barbital (Barb), and EtOH. The development of physical dependence on Mor, Barb, and EtOH was not modified by the pretreatment with other drugs. These results may serve to predict the risk of the interactions between various dependence-liable drugs in humans.
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PMID:[Pharmacological interactions between dependence-liable drugs]. 325 Jan 53

Kyotorphin (Tyr-Arg) is a unique neuropeptide which produces analgesia by releasing Met-enkephalin from slices of the brain and spinal cord. Recent studies revealed that kyotorphin possesses the properties of neurotransmitter/neuroregulator. In the present study, we identified a kyotorphin synthetase in the soluble fraction of rat brain synaptosomes (synaptosol) and characterized it. The enzyme partially purified with Sephacryl S-300 showed an absolute requirement for ATP, MgCl2, tyrosine, and arginine. The optimal pH was 7.5-9.0 and the pI was determined to be 6.1-6.2 by isoelectric focusing. The Km was 25.6 microM for tyrosine, 926 microM for arginine, 294 microM for ATP, and 442 microM for MgCl2. The Vmax was 34.0 pmol/mg of protein/h. The apparent molecular size of this "kyotorphin synthetase" further purified by the DE52 column was 240,000-245,000 daltons, estimated using TSKgel G4000SW column chromatography. The enzyme reaction is represented by the following equation: Tyr + Arg + ATP + MgCl2 + kyotorphin synthetase----Tyr-Arg (kyotorphin) + AMP + PPi + MgCl2 + kyotorphin synthetase. The regional distribution and subcellular localization of the synthetase showed a close correlation to that of kyotorphin levels in the rat brain. The amounts of kyotorphin formed from amino acids by the synthetase in the dialyzed synaptosol was 3.0-4.0 times higher than that from precursor proteins by processing enzymes within the 30 min incubation.
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PMID:Kyotorphin (tyrosine-arginine) synthetase in rat brain synaptosomes. 359 66


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