Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Numerous reports indicated that substance p (SP) was a neurotransmitter involved in nociception, it also had analgesic effects in the most part of the central nervous system of all mammals, including man. The numbers of mast cell in human's some acupoint tissue were much higher than the non-acupoint tissue, there was connection between the nerves and mast cells which contained SP particles. Therefore, it is worth studying the change of the concentration of SP in the skin and plasma of rats during the process of acupuncture analgesia. 55 rats were divided into 8 groups; (1) Control group; (2) Heat stimulation group; (3) Electro-acupuncture group; (4) Morphine group; (5) Naloxone (NX) group; (6) NX plus electro-acupuncture group; (7) Non-acupoint electro-acupuncture group; (8) Normal saline solution group. The concentration of SP in the "channel" "acupoint" skin and plasma of rats were determined by radioimmunoassay (RIA). The results show that after acupuncture, the tail-flick threshold is increased, the concentration of SP in the skin and plasma is decreased significantly and the effect of electro-acupuncture is abolished by naloxone (i.p). The results suggest that SP is a transmitter relating to skin nociception and involves the process of pain regulation. Electro-acupuncture can inhibit SP release from the skin and the plasma of rats. There is a functional interaction between SP and endorphin in the effects of electro-acupuncture. That is the SP decreased induced by electro-acupuncture may depend upon the function of opiate receptors.
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PMID:[The change of the concentration of substance P in the rats "channel" "point" skin and plasma in the acupuncture analgesia]. 248 85

Enkephalins are a biochemical pathway for endogenous analgesia. A number of compounds inhibit degradation of enkephalins within the body. One of these compounds, D-phenylalanine (DPA), has been shown to increase the pain threshold in animals. It is hypothesized that this naloxone reversible analgesia is induced by DPA blockage of enkephalin degradation by the enzyme carboxypeptidase A. Preliminary studies of chronic pain patients have shown a response rate to DPA from 32% to 75%. This study was a double-blind crossover evaluation of a randomized parallel design to determine the efficacy of DPA in 30 subjects with chronic pain from varied etiology which was unrelieved by multiple therapeutic interventions. Each patient received a stabilized therapeutic regimen during this study consisting of four weeks of either DPA 250 mg or lactose (placebo) orally four times a day. After four weeks the DPA and placebo groups were crossed over for an additional four weeks of treatment. Pain was quantified using a visual analog pain scale and a cold pressor test. Data from the pain questionnaires revealed more pain relief on DPA reported by 25% of the patients, more pain relief on placebo reported by 22% of the patients, and no difference in pain relief reported by 53% of the patients. Lowest pain level of the visual analog scale was reported by 47% of the patients on DPA and 53% on placebo. There appears to be no significant analgesic effect from D-phenylalanine in chronic pain patients when compared to placebo.
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PMID:Analgesic effectiveness of D-phenylalanine in chronic pain patients. 352 9

The effect of D-Phenylalanine (D-Phe), putative carboxypeptidase A inhibitor and its four derivatives (T1-T4) on analgesia, development of tolerance and physical dependence to morphine, and on degradation of both exogenous and endogenous enkephalins was investigated. Systemic administration of either D-Phe or its derivatives produced naloxone-reversible analgesia in the hot-plate test in mice. Naloxone-precipitated morphine withdrawal syndrome was attenuated in mice after systemic subacute administration (7 days, 1.2 mmol/kg, sc) of D-phe derivatives, the development of tolerance to morphine being unchanged. In the presence of either D-Phe or its derivatives in incubation mixture (up to 10(-3) mol/l) the hydrolysis of exogenous 3H-Met5-and 3H-Leu5-enkephalin in striatal homogenates was slightly inhibited. Moreover, the addition of D-Phe or its derivatives seemed to increase the per cent of recovered endogenous Met5-enkephalin released from veratridine-depolarized striatal particles. In contrast, bestatin, an amino-peptidase inhibitor, and a mixture of dipeptides (Tyr-Tyr, Leu-Leu, Leu-Gly) markedly inhibited degradation of both endogenous and exogenous enkephalins in vitro. The results obtained in this study suggest that that pharmacological activity of D-Phe is not directly related to the endogenous opiate system.
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PMID:The effects of D-phenylalanine and its derivatives on enkephalin degradation in vitro: relation to analgesia and attenuation of the morphine withdrawal syndrome. 376 85

It had previously been shown that D-phenylalanine and hydrocinnamic acid, two in vitro inhibitors of carboxypeptidase A, possess an analgesic action when injected i.p. in mice. We have studied the in vivo effects of indole-3-acetic acid, another carboxypeptidase A inhibitor, and of the following analogs of D-phenylalanine substituted in position 4: D-tyrosine, p-fluoro-D-phenylalanine and trifluoroacetyl-p-fluoro-D-phenylalanine. Whereas indole-3-acetic acid caused a higher and shorter analgesia in comparison with D-phenylalanine, p-fluoro-D-phenylalanine and its N-trifluoroacetyl derivative yielded both a greater and a much longer lasting analgesic effect. Since the latter compound showed only slight inhibitory activity on carboxypeptidase A in vitro, we suggest that inhibition of this enzyme and analgesia might not be directly correlated.
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PMID:Antinociceptive effect of some carboxypeptidase A inhibitors in comparison with D-phenylalanine. 407 40

The recently discovered native endomorphins play an important role in opioid analgesia, but their metabolic fate in the organism remains relatively little known. This paper describes the application of high-performance liquid chromatography combined with electrospray ionization mass spectrometry to identify the degradation products resulting from the incubation of endomorphins with proteolytic enzymes. The native endomorphin-1, H-Tyr-Pro-Trp-Phe-NH2 (1), and endomorphin-2, H-Tyr-Pro-Phe-Phe-NH2 (2), and an analog of endomorphin-2, H-Tyr-Pro-Phe-Phe-OH (3), were synthetized, and the levels of their resistance against carboxypeptidase A, carboxypeptidase Y, aminopeptidase M and proteinase A were determined. The patterns of peptide metabolites identified by this method indicated that carboxypeptidase Y first hydrolyzes the C-terminal amide group to a carboxy group, and then splits the peptides at the Trp3-Phe4 or Phe3-Phe4 bond. The remaining fragment peptides are stable against the enzymes investigated. Carboxypeptidase A degrades only analog 3 at the Phe3-Phe4 bond. Aminopeptidase M cleaves the peptides at the Pro2-Trp3 or Pro2-Phe3 bond. The C-terminal fragments hydrolyze further, giving amino acids and Phe-NH2-s while the N-terminal part displays a resistance to further aminopeptidase M digestion. Proteinase A exhibits a similar effect to carboxypeptidase Y: the C-terminal amide group is first converted to a carboxy group, and one amino acid is then split off from the C-terminal side.
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PMID:Liquid chromatographic study of the enzymatic degradation of endomorphins, with identification by electrospray ionization mass spectrometry. 1042 May 97

Analgesia is an important physiological function of the endocannabinoid system and one of significant clinical relevance. This review discusses the analgesic effects of endocannabinoids at spinal and peripheral levels, firstly by describing the physiological framework for analgesia and secondly by reviewing the evidence for analgesic effects of endocannabinoids obtained using animal models of clinical pain conditions. In the spinal cord, CB(1) receptors have been demonstrated in laminae of the dorsal horn intimately concerned with the processing of nociceptive information and the modulation thereof. Similarly, CB(1) receptors have been demonstrated on the cell bodies of primary afferent neurones; however, the exact phenotype of cells which express this receptor requires further elucidation. Local administration, peptide release and electrophysiological studies support the concept of spinally mediated endocannabinoid-induced analgesia. Whilst a proportion of the peripheral analgesic effect of endocannabinoids can be attributed to a neuronal mechanism acting through CB(1) receptors expressed by primary afferent neurones, the antiinflammatory actions of endocannabinoids, mediated through CB(2) receptors, also appears to contribute to local analgesic effects. Possible mechanisms of this CB(2)-mediated effect include the attenuation of NGF-induced mast cell degranulation and of neutrophil accumulation, both of which are processes known to contribute to the generation of inflammatory hyperalgesia. The analgesic effects of cannabinoids have been demonstrated in models of somatic and visceral inflammatory pain and of neuropathic pain, the latter being an important area of therapeutic need. Analgesia is one of the principal therapeutic targets of cannabinoids. This review will discuss the analgesic effects of endocannabinoids in relation to two areas of therapeutic need, persistent inflammation and neuropathic pain. The more general aspects of the role of cannabinoids, endogenous and exogenous, in analgesia have been recently reviewed elsewhere (Rice, Curr Opi Invest Drugs 2001; 2: 399-414; Pertwee, Prog Neurobil 2001; 63: 569-611; Rice, Mackie, In: Evers A. S, ed. Anesthetic Pharmacology: Physiologic Principles and Clinical Practice. St. Louis: Harcourt Health Sciences, 2002). Since a major goal in the development of cannabinoid-based analgesics is to divorce the antinociceptive effects from the psychotrophic effects, the discussion will focus on the antinociceptive effects produced at the spinal cord and/or peripheral level as these areas are the most attractive targets in this regard. A mechanistic discussion of the "framework" for analgesia will be followed by a description of studies examining the role of endocannabinoids in relieving pain; since the elucidation of these effects was undertaken using synthetic cannabinoids, reference will also be made to such studies, in the context of endocannabinoids.
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PMID:Endocannabinoids and pain: spinal and peripheral analgesia in inflammation and neuropathy. 1205 40

Mastocytosis is a heterogeneous group of clinical disorders characterized by an excessive number of normal mast cells in a variety of tissues (skin, bone marrow, liver, spleen and lymph nodes). It is most often seen in the skin in pediatric-onset mastocytosis presenting as urticaria pigmentosa. Children with this disorder are on a strict avoidance protocol of triggering factors to decrease the likelihood of life-threatening anaphylactic reactions. Close monitoring and the avoidance of known histamine-releasing drugs is necessary in the pediatric dental office, as is a readiness to use resuscitative measures. A case of a 4-year, 6-month-old pediatric dental patient with mastocytosis is presented. Dental treatment was provided in an ambulatory setting utilizing nitrous oxide, oxygen analgesia and H1 and H2 antihistamines to prevent mast cell degranulation and to provide sedation.
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PMID:Dental management of a pediatric patient with mastocytosis: a case report. 1221 79

The analgesic and anti-inflammatory effects of subcutaneously administered bupivacaine, morphine and tramadol on formalin-induced inflammation were compared. 0.25 % bupivacaine in Group B, 20 mg/kg tramadol in Group T, 1 mg/kg morphine in Group M and 0.9 % NaCl in Group S in a volume of 200 micro l were injected into the right hind paw of the rats (n: 40) 15 minutes before injection of 50 micro l 5 % formalin. Sedation and pain behaviour scores, number of flinches and licking-time were recorded. The degree of dermal edema, intraneural edema, vasodilation, erythrodiapedesis, infiltration of polymorphonuclear leukocyte/lymphocyte and mast cell counts were analyzed histopathologically. In Group T and B, circumferential changes were lower than in Group M and S. The pain behaviour scores were significantly lower in Group T and B. The number of flinches in Group T was lower than Group B and S. The vasodilation was significant only in Group M. The dermal edema was limited to deep dermis only in Group T. Preinflammational subcutaneous tramadol infiltration can provide effective analgesia and may have anti-inflammatory effects.
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PMID:The analgesic and anti-inflammatory effects of subcutaneous bupivacaine, morphine and tramadol in rats. 1538 6

Cannabis extracts and synthetic cannabinoids are still widely considered illegal substances. Preclinical and clinical studies have suggested that they may result useful to treat diverse diseases, including those related with acute or chronic pain. The discovery of cannabinoid receptors, their endogenous ligands, and the machinery for the synthesis, transport, and degradation of these retrograde messengers, has equipped us with neurochemical tools for novel drug design. Agonist-activated cannabinoid receptors, modulate nociceptive thresholds, inhibit release of pro-inflammatory molecules, and display synergistic effects with other systems that influence analgesia, especially the endogenous opioid system. Cannabinoid receptor agonists have shown therapeutic value against inflammatory and neuropathic pains, conditions that are often refractory to therapy. Although the psychoactive effects of these substances have limited clinical progress to study cannabinoid actions in pain mechanisms, preclinical research is progressing rapidly. For example, CB(1)mediated suppression of mast cell activation responses, CB(2)-mediated indirect stimulation of opioid receptors located in primary afferent pathways, and the discovery of inhibitors for either the transporters or the enzymes degrading endocannabinoids, are recent findings that suggest new therapeutic approaches to avoid central nervous system side effects. In this review, we will examine promising indications of cannabinoid receptor agonists to alleviate acute and chronic pain episodes. Recently, Cannabis sativa extracts, containing known doses of tetrahydrocannabinol and cannabidiol, have granted approval in Canada for the relief of neuropathic pain in multiple sclerosis. Further double-blind placebo-controlled clinical trials are needed to evaluate the potential therapeutic effectiveness of various cannabinoid agonists-based medications for controlling different types of pain.
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PMID:Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes. 1861 44

Mastocytosis is a rare disorder caused by the proliferation and accumulation of mast cells in various organs. It has a broad variety of clinical manifestations, including cardiovascular collapse. Diverse stimuli trigger the release of vasoactive substances and parturients with systemic mastocytosis are at high risk for precipitating mast cell degranulation. As a result, women with systemic mastocytosis should have an anaesthetic plan for labour and delivery. Anxiety, stress, sleep deprivation, pain and numerous pharmacological agents are all triggers for mast cell degranulation. For pain relief in labour, epidural analgesia is recommended. Pharmacological agents with a high potential for triggering mast cell degranulation should be avoided. This is particularly important in the case of an emergency caesarean section. Resuscitation equipment must be available should life-threatening haemodynamic instability occur during surgery. We report the case of a pregnant woman with systemic mastocytosis who required emergency caesarean section.
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PMID:Anaesthetic management of emergency caesarean section in a parturient with systemic mastocytosis. 2370 36


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