Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.5.4.17 (adenosine deaminase)
5,206 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experiments over the past decade have revealed a third component in the autonomic nervous system which is neither adrenergic nor cholinergic. These nerves are strongly represented in the gastrointestinal tract of a wide range of vertebrate species and have also been identified in lung, trachea, retractor penis, bladder, oesophagus, eye, seminal vesicle and in some parts of the cardiovascular system and brain. Evidence has been presented that the principal active substance released by these nerves in the gut is a purine nucleotide, probably ATP, and they have therefore been termed 'purinergic'. The evidence includes: (1) synthesis and storage of ATP in nerves; (2) release of ATP from the nerves when they are stimulated; (3) mimicry by exogenously applied ATP of the action of nerve-released transmitter; (4) the presence of Mg2+-activated ATPase, 5'-nucleotidase and adenosine deaminase, enzymes which inactivate ATP; (5) the similar blocking and potentiating effects produced by drugs on the responses to exogenously applied ATP and nerve stimulation. A tentative model for the synthesis, storage, release and inactivation of ATP during purinergic nerve transmission is proposed. Some properties of purinergic receptors are described.
...
PMID:The purinergic nerve hypothesis. 2 31

Cessation of perivascular nerve stimulation (NS) elicits a transient increase in intestinal blood flow above the prestimulatory value. This enhancement of blood flow constitutes the phenomenon of post-nerve stimulation hyperemia (PSH). We investigated the involvement of peptidergic sensory nerves in intestinal PSH. In anesthetized rats the velocity of blood flowing through the anterior mesenteric artery (VBF) was measured with a pulsed Doppler velocimeter. PSH was induced by 4 min of postganglionic electrical NS (5 Hz). PSH was abolished by distal periarterial application of tetrodotoxin and intra-arterial lidocaine, which suggests a peripheral sensory nervous mechanism for PSH. The increase in conductance at peak PSH was blocked by pretreatment with the selective, primary afferent neurotoxin capsaicin administered as 1) subcutaneous injection in neonatal life, 2) topical application to periarterial nerves, or 3) injection into the jejunal lumen. In rats pretreated with reserpine, NS evoked a hyperemic response, which was blocked by capsaicin. Treatment with adenosine deaminase inhibited PSH considerably less than capsaicin, suggesting a lesser role for adenosine in PSH. Our findings support the hypothesis that postganglionic NS activates both adrenergic and peptidergic nerves and that the latter release vasodilator peptides in the gut during PSH.
...
PMID:Peptidergic nerves mediate post-nerve stimulation hyperemia in rat gut. 163 13

This study was designed to evaluate the role of adenosine and adenosine receptors in the reactive (RH) and functional hyperemia (FH) in rat gut. Experiments were performed on anesthetized rats. Mesenteric blood flow was measured with a pulsed Doppler flowmeter. We also determined the duration of reactive hyperemia, excess volume of blood flow above control value and maximal increase in mesenteric vascular conductance during both hyperemic responses. Data were collected following release from occlusions lasting 30, 60 and 120 sec. Functional hyperemia was induced by perfusion of the gut with a solution. Studied parameters were obtain before and after adenosine deaminase (ADA) and two adenosine receptor antagonists: 8-phenyltheophylline (8-PT) and 1.3-dipropyl-7-methyl-xanthine (DPMX). In fasted rats ADA and 8-PT reduced of RH after each period of occlusion and DPMX was ineffective in reducing any parameter of RH. In fed rats control mesenteric blood flow was increased. ADA, 8-PT, and DPMX were more effective inhibitors of RH and FH. Above findings suggest that adenosine play a role in the modulation of RH and FH acting on A2 subtype receptors.
...
PMID:[Role of adenosine in functional and reactive intestinal hyperemia]. 184 31

The distribution of the potent inhibitor of adenosine deaminase (ADA), 2'-deoxycoformycin (DCF), in the brain of the rat and its inhibition of ADA in brain and gut was determined. The accumulation of [3H]DCF in brain was maximal 2 hr after intraperitoneal injection and elimination was best described by a two compartment model having t1/2 phases of about 1-5 hr and 50 hr. The activity of ADA in gut exhibited dose-related inhibition at 1.9, 3.7 and 18.6 mumol/kg (i.p.) and returned to normal by 16 days. In brain, ADA was inhibited by about 95% at all three of these doses of DCF 2 hr after injection and activity returned to control levels by 30 days with the two smaller doses, but remained at 66% of control levels at 50 days with 18.6 mumol/kg. The t1/2 of the recovery of the activity of ADA in both brain and gut was found to be dose-dependent. The failure of the activity of ADA in brain to recover after treatment with 18.6 mumol/kg suggests either long-term down-regulation of the expression of ADA or irreversible damage to ADA-containing neurons.
...
PMID:Pharmacokinetics of 2'-deoxycoformycin, an inhibitor of adenosine deaminase, in the rat. 349 81

We previously have shown that aging alters the expression of several intestinal enzymes during cell migration from the crypt base to the villus tip. The activities of many mucosal enzymes are dramatically altered by starvation and refeeding. We compared the effects of starvation and refeeding on the activities of selected intestinal enzymes in young and aging Fischer 344 rats. Gut mass fell during starvation and rose during refeeding to a similar extent in both groups. Sucrase and maltase specific activities in control aging rats were lower than in young controls and, during starvation, enzyme activities declined at approximately similar rates in both groups. Total duodenal enzyme activities fell by about two-thirds in young animals and by greater than 80% in aged animals. Alkaline phosphatase and adenosine deaminase activities also were lower in aging than young animals. During refeeding, enzyme activities rose more in aging rats than in the young. In fact, the specific activities of sucrase and maltase in aging rats refed for 1 day exceeded the values found in fed aging controls. The adaptive responses of duodenal enzymes exceeded those in the jejunum. In conclusion, the aging intestine responds appropriately to starvation and refeeding. However, the fluctuations in brush-border enzyme activities are much greater in aging than in young rats. Such alterations may be an important influence of aging on gut differentiation and might have an adverse impact upon nutritional maintenance in aging animals.
...
PMID:Adaptive changes of intestinal enzymes to nutritional intake in the aging rat. 359 66

Two main candidates, adenosine 5'-triphosphate (ATP) and vasoactive intestinal peptide (VIP), have been proposed as inhibitory transmitters at neuromuscular junctions in the gut. We have used a photoaffinity analogue of ATP, 3'-O-(4-benzoyl)benzoyl ATP or BzATP, that binds covalently to ATP receptors and inactivates them in the presence of light and a specific high-affinity VIP antiserum in order to examine the contributions of ATP and VIP to neurally induced relaxation in circular smooth muscle of the gastric fundus of the guinea pig. VIP and ATP caused dose-dependent relaxation; the effect of ATP was equal to that of its stable isostere, alpha, beta-methylene ATP, and was resistant to degradation by adenosine deaminase, indicating interaction of ATP with purinergic P2-receptors. Relaxation induced by VIP was selectively inhibited by VIP antiserum (final dilution 1:120), while that induced by ATP was selectively inhibited by photoactivated BzATP. Relaxation induced by electrical field (i.e., neural) stimulation was inhibited by VIP antiserum only; photoactivated BzATP had no effect. Inhibition of neurally induced relaxation ranged from 86% (P less than 0.01) at the lowest frequencies to 34% (P less than 0.01) at the highest frequencies. Maximal field stimulation caused an 11-fold increase in VIP release from intramural neurons. The results strongly favor VIP as the neural mediator of gastric relaxation.
...
PMID:Vasoactive intestinal peptide as a neural mediator of gastric relaxation. 396 63

Gastrointestinal and peritoneal tuberculosis remain common problems in impoverished areas of the world, but is relatively infrequent in the United States. A resurgence of tuberculosis in America since the mid-1980s means that clinicians will continue to see cases. Immigrants and AIDS patients are two population groups at particular risk for abdominal tuberculosis in this country; the urban poor, the elderly, and Indians on reservations are others. The symptoms and signs of GI and peritoneal tuberculosis are nonspecific, and unless a high index of suspicion is maintained, the diagnosis can be missed or delayed resulting in increased morbidity and mortality. Only 15-20% of patients have concomitant active pulmonary tuberculosis. Tuberculous peritonitis needs to be considered in all cases of unexplained exudative ascites. Laparoscopy with directed biopsy currently is the best way to make a rapid specific diagnosis. The measurement of ascites adenosine deaminase levels represents a major diagnostic advance in tuberculous peritonitis, particularly in underdeveloped areas where the affliction is common and laparoscopy may not be available. With greater experience, this testing procedure could also supersede invasive studies in western countries, particularly in high-risk patient groups. The commonest sites of tuberculous involvement of the GI tract are the ileocecal area, the ileum and the colon, although any area of the gut can be involved. If the area of affected gut is within reach of the flexible endoscope, rapid diagnosis may be possible with biopsy (if acid-fast bacilli or caseating granulomas are seen). Not infrequently, the disease is not considered until it is diagnosed at the time of surgery. In countries with a high prevalence of intestinal tuberculosis, a therapeutic trial of antituberculous drugs may be reasonable if the clinical picture is compatible. The diagnosis of tuberculous enteritis can be taken as highly probable if the patient responds to treatment and this is followed by no recurrence. Serologic tests for diagnosing tuberculosis are being improved and evaluated in intestinal tuberculosis. Gastrointestinal and peritoneal tuberculosis are treated with antituberculous drugs. Surgery is reserved for complications or uncertainty in diagnosis. Six-, 9-, and 18- to 24-month regimens are all effective for extrapulmonary tuberculosis. Standard therapy of at least 9 months duration is also effective in most AIDS patients who are started on appropriate treatment in a timely fashion and who are compliant. The potential for multidrug resistance needs to be kept in mind and accounted for.
...
PMID:Tuberculosis of the gastrointestinal tract and peritoneum. 831 33

Intestinal reactive hyperemia is an abrupt blood flow increase following release from anterior mesenteric arterial occlusion. We investigated the role of adenosine in reactive hyperemia. In anesthetized rats, mesenteric arterial velocity of blood flow was determined with pulsed Doppler velocimetry and arterial pressure with a transducer. Three indices quantifying reactive hyperemias obtained following 30, 60, and 120 s arterial occlusions included duration, the volume of blood flow exceeding preocclusion blood flow, and the percentage increase in conductance. In six rat groups (half fasted and half with intrajejunal bile-oleate solutions), hyperemia parameters were determined before and after administration of either adenosine deaminase (ADA) or two adenosine receptor antagonists, namely 8-phenyltheophylline (8-PT) and 1,3-dipropyl-7-methylxanthine (DPMX). In fasted gut the three agents had variable effectiveness against reactive hyperemia, although 8-PT was the most consistent inhibitor. Instillation of intrajejunal lipid evoked a stable hyperemia and increased duration and blood flow volume after each occlusive period. ADA and 8-PT were more effective against reactive hyperemia in fed gut than in fasted gut. Our findings suggest that adenosine is a vasodilator metabolite modulating mesenteric reactive hyperemia, especially during enhanced intestinal metabolic activity.
...
PMID:Adenosine modulates reactive hyperemia in rat gut. 835 49

Non-adrenergic, non-cholinergic (NANC) nerve stimulation results in excitation (e.j.p., rebound depolarization, contractions) or inhibition (i.j.p., afterhyperpolarization, relaxations) of the gut. NANC neuronal mechanisms participate in the maintenance of the basal tone and spontaneous activity of the gut. There are however species differences, i.e. both NANC excitation and inhibition are present in the guinea pig and only NANC inhibition in the rat intestine. Substance P-like neuropeptide/s are suggested to be mediators released from excitatory NANC and sensory nerves. The latter are activated by histamine and degenerated by capsaicin. There is evidence in favor of a nitric oxide-like substance rather than ATP, dopamine, GABA and neuropeptides (e.g. VIP, PHI/PHM) as the inhibitory NANC mediator in the gut. TTX, high Mg(2+)-low Ca2+ media, 3,4-diaminopyridine, dipyridamol and adenosine deaminase modulate NANC excitation and inhibition. The NANC excitation is more sensitive than the NANC inhibition to the action of catecholamines, reserpine, 6-hydroxydopamine, chymotrypsin, prednisolon, bacitracin, opioids, free oxygen species and low concentration of local anesthetics.
...
PMID:NANC transmission in intestines and its pharmacological modulation. 839 Nov 98

We have shown recently that adenosine deaminase (ADA)-deficient mice die perinatally with severe liver cell degeneration. In addition to enzyme substitution, we report the restoration of viability through introduction of the human ADA gene. The ADA gene is subject to complex developmental and tissue-specific regulation. To include the cis-regulatory elements necessary for correct regulation of the human ADA gene, a large transgenic locus constituting the human ADA gene with 10 kb of 5' and 4 kb of 3' flanking sequences was generated by co-injection of two overlapping DNA fragments into murine zygotes. Probably as a result of extrachromosomal (homologous) recombination between the fragments, one of the two transgenic lines contained a reconstituted, functional human ADA gene. As in man, human ADA expression generally was low in these transgenic mice, but high in the thymus, spleen and gastro-duodenal part of the gut. Apparently, all cis-regulatory elements essential for a human expression pattern were incorporated in the transgene and were functional in the murine background. Similarly to man, the upper alimentary tract of the transgenic mice revealed low human ADA activity in contrast to extremely high levels of murine ADA. The human gene probably lacks the cis-regulatory elements that target high level murine ADA expression to the murine upper alimentary tract. ADA-deficient mice rescued by introduction of the human ADA transgene appeared histologically and immunologically normal. Apparently, human ADA can complement murine ADA in all tissues, even in the epithelium of the upper alimentary tract where human ADA activity is as much as 70-fold lower than murine ADA activity in wild-type mice. Clearly, the lethal phenotype of ADA-deficient mice is due to the absence of ADA.
...
PMID:Full genetic rescue of adenosine deaminase-deficient mice through introduction of the human gene. 889 85


1 2 3 Next >>

---