Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of estradiol (1 microgram: E-1) treatment on uterine hyperemia and uterine sensitivity to various biogenic compounds were evaluated in ovariectomized (OVX) animals treated with either sesame oil or E-1 for 3 days. The E-1 treatments induced significant elevations in uterine weight, blood flow, and alpha- and beta-receptor numbers as compared with oil-treated controls. In contrast, uterine norepinephrine (NE) levels were reduced in E-1-treated, OVX guinea pigs as compared with oil-treated controls. Uterine sensitivity and responsivity to NE (10(-6) M) and acetylcholine (ACH: 10(-8) M) were either comparable to, or enhanced, in E-1-treated animals as compared with controls. In particular, combined ACH-NE treatment induced a dramatic increase in contraction force in E-1-treated uteri as compared with uteri from oil-treated animals. The use of specific adrenergic alpha- (phentolamine: 10(-6) M) or beta- (propranolol: 10(-6) M) receptor blocking agents indicated that the estrogenic response was mediated via the alpha-adrenergic receptor complex. Since atropine (10(-8) M) effectively blocked the cholinergic accentuation of this uterine response, it is suggested that a cholinergic priming, or beta-receptor block, is necessary for the full expression of the alpha-adrenergic-mediated, estrogenic response in the guinea pig. The estrogen-associated increase in available alpha- and beta-receptors and depressed tissue NE levels probably account for both the hyperemic response and enhanced tissue sensitivity to biogenic compounds in the guinea pig.
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PMID:Regulation of estrogen-induced uterine hyperemia and contractility in the guinea pig: cholinergic modulation of an alpha-adrenergic response. 632 35

The influence of cardiac cholinergic activation was studied in rats and cats on the induction and maintenance of ventricular fibrillation (VF). Acetylcholine (ACH 2-25 micrograms/kg), in doses which did not cause bradycardia or hypotension, induced appearance of spontaneous VF (duration 2-60 sec.) in 9/20 rats which have a high sympathetic autoregulation and in 3/6 cats only, 20-40 secs after the latter had been given adrenaline. ACh (10-45 micrograms/kg) and methacholine (10-40 micrograms/kg) also significantly prolonged the fibrillatory period induced electrically in cats and rats with and without atrial or ventricular pacing. The induction or prolongation of VF did not occur when higher doses of ACh (50-100 micrograms/kg) were given to rats. The influence of moderate amounts of cholinergic agents on the heart may be due to localised effects resulting in asynchronous activity. Alternatively, they may produce a discharge of multiple ectopic pacemakers or a disturbance in impulse conduction. Higher doses of ACh depress the S-A and ventricular ectopic activity node thereby decreasing the probability of inducing VF. It is concluded that under conditions of raised cardiac adrenergic activity, a moderate increase in cholinergic influence can both induce and prolong VF. The relevance of these findings to the "sudden infant death" syndrome is discussed.
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PMID:The influence of cardiac cholinergic activation on the induction and maintenance of ventricular fibrillation. 639 60

The possible immunological mechanisms involved in the progression from acute type B hepatitis to chronic hepatitis can be summarised as follows: following replication of the virus in the hepatocyte nucleus, the surface coat is added and the virus released from the hepatocyte. T cells recognise the foreign viral antigen on the surface of the liver cells and mount a T cell mediated reaction against infected hepatocytes. They also stimulate B cells to produce antibody to LSP, the ensuing antibody-dependent cell-mediated K cell reaction against normal liver membrane antigens contributing to the hepatocyte necrosis. Released virus stimulates anti-viral antibody production which complexes with the virus, the complex being removed by the reticuloendothelial system. With the removal of virus there is no longer any T cell reaction against the virus or helper effect for anti-LSP production and this, together with a normally functioning suppressor T cell system, leads to cessation of liver cell necrosis and recovery from the episode of acute hepatitis. In HBsAg-positive ACH as a result of a quantitative or qualitative defect in the production of antibody to Dane particles there is a failure to clear the virus, with reinfection of further hepatocytes and continuation of both mechanisms of immunological liver cell damage. In patients progressing to HBsAg-negative ACH, however, anti-viral antibody production is adequate and the virus is cleared. In this group of patients the defect probably lies in suppressor T cell function, which is unable to switch off the autoimmune reaction against LSP. The increased frequency of histocompatibility antigens HLA A1 and B8 and the associated high levels of autoantibodies and anti-viral antibodies suggests that this defect may be genetically inherited.
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PMID:Pathogenesis of active chronic hepatitis. 644 63

Development has been studied in re-aggregate cultures derived from the 16 day foetal rat brain and the effects of triiodothyronine (T3) investigated. Cultures were maintained in either a medium containing 10% serum (S+), or in serum-free culture medium (S-) or in serum-free medium containing 30nM T3. The muscarinic cholinoceptor, measured by specific binding of [3H]-quinuclidinyl benzitate ([3H]-QNB) at 9 and 14 days in vitro, was at a lower level in the serum-free cultured cells compared with those in serum-containing culture medium (S+). In cultures in the latter medium, receptor concentration at day 14 was of a similar magnitude to that in rat brain at an equivalent postnatal age. Binding increased with development from 9 to 14 days in vitro in the S+ medium but not in the S- medium. T3 treatment caused an 85% increase in [3H]-QNB binding compared with the cultures in S- medium at day 14 to a level equivalent to that found in the cells grown in S+ medium. This increase was reflected in the Bmax but not in the KD (approx. 0.1nM). Choline acetyltransferase (ChAT) activity developed more slowly in the S- medium than in the S+ medium where the specific activity approximated values obtained in vivo. T3 treatment of cultures grow in S- medium significantly enhanced the developmental rate of increase of ChAT activity. The characteristics of [3H]-choline uptake and metabolism in the cultures was examined. Uptake was strictly Na+-independent but was energy-dependent, and inhibited by 2, 4'-dinitrophenol (2, 4'-DNP) and cooling (0-4 degrees C). Neither iodoacetate nor ouabain had any effect on the amount of uptake. Hemicholinium (HC3) was a potent inhibitor of uptake (70% inhibition at 10 microM HC3). Metabolism studies showed virtually no conversion to [3H]-acetylcholine ([3H]-ACH) in reaggregates grown in either the S+, S- or T3 containing media. However, a small amount of [3H]-choline was incorporated into phosphorylcholine. T3 treatment had no effect on this metabolic profile. The kinetics of [3H]-choline uptake by the re-aggregates was also studied in the re-aggregate cultures (after 12 and 22 days in vitro) using [3H]-choline at 0.05-100 microM. Both Eadie-Hofstee transformation and least-squares analysis of the data showed that the uptake comprised only a single low-affinity component with an apparent Kt = approx. 50 microM. Unlike ChAT and [3H]-QNB binding, there appeared to be no difference between the uptake in the different culture conditions. 6 It is concluded that the differentiation of cholinergic neurones and muscarinic receptors in serum-free cultured re-aggregates from foetal rat brain is enhanced by thyroid hormone treatment. The development of [3H]-choline uptake does not seem to be associated with cholinergic cells under these culture conditions, and is unaffected by thyroid hormone treatment.
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PMID:Development of markers for cholinergic neurones in re-aggregate cultures of foetal rat whole brain in serum-containing and serum-free media: effects of triiodothyronine (T3). 648 98

The influence of a minimal surgical transection around the trachea on ACH- and allergen-induced bronchoconstriction was studied in a series of 21 cats. A significant smaller bronchoconstriction was observed after surgical transection around the trachea. The trachea isolation itself induced a smaller nonsignificant bronchoconstrictive response. This diminished response of the airways after this surgical intervention assumes an interruption of syncytial connections, which alters the response to bronchoconstricting stimuli of the whole bronchial system. The exact role of these syncytial connections has yet to be clarified.
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PMID:Influence of a minimal surgical transection around the trachea on bronchoconstriction in cats. 649 8

In man, the influence of calcium entry blockers (CEB) on nonspecific bronchial sensitivity and resting bronchial tone is controversial. In 10 asthmatic and 8 normal subjects we recorded specific airway conductance (Gaw/VL) and flow volume loops before, 30, 60, and 90 min after the inhalation of saline, 10 (V10) and 20 mg (V20) of verapamil. The dose of inhaled histamine and acetylcholine producing Gaw/VL of -40% (PD40H and PD40ACH, respectively) with and without pretreatment with saline, V10, and, in 15 subjects, V20 was also determined. We measured plasma verapamil concentrations immediately after the end of nebulization of V10 and V20, and 30 and 60 min later. In normal subjects, V10 and V20 produced a maximal % delta Gaw/VL of 22.30 (+/- 19.50) and 33.00 (+/- 15.82), respectively (p less than 0.05). In asthmatics, V10 and V20 produced comparable % delta Gaw/VL of 22.00 (+/- 22.50) and 38.60 (+/- 38.60), respectively. This bronchodilating effect involved predominantly the large airways, persisted for 60 to 90 min, was reproducible, affected only some subjects (11 of 18), and was independent of the resting Gaw/VL, degree of bronchial sensitivity to H and ACH, and the time course of plasma verapamil concentration. The latter reached a maximum of 24.3 +/- 7.1 ng/ml after V20. In both normal and asthmatic subjects, saline or V10 did not significantly alter PD40H and PD40ACH. In normal subjects, pretreatment with V20 increased PD40H 5.3 times and PD40ACH 3.22 times (p less than 0.05). Except in 2 asthmatics, in whom V20 decreased PD40 and PD40ACH, it increased significantly PD40ACH (dose ratio: 3.15, p less than 0.05) but not PD40H.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of inhaled verapamil on resting bronchial tone and airway contractions induced by histamine and acetylcholine in normal and asthmatic subjects. 650 96

The effects of Hi and ACH aerosol and of intravenous infusion of compound 48/80 on bronchoconstriction and plasma levels of Hi, TXB2, KH2PGF2 alpha and KH2PGE2 were investigated in 11 bastard dogs. Administration of Hi and ACH aerosol induced bronchoconstriction accompanied by an increase in the plasma levels of Hi and TXB2. No effect on the plasma levels of KH2PGF2 alpha and KH2PGE2 was detected. Release of endogenous Hi by compound 48/80 induced bronchoconstriction and significant increases in the plasma levels of TXB2 as well as of KH2PGF2 alpha and KH2PGE2. The effects of a second administration of Hi and ACH aerosols after compound 48/80 did not differ qualitatively from the effects of the first aerosol administration. However, quantitatively, the second Hi aerosol induced significantly less bronchoconstriction and TXB2 release. Similarly, effects of the second ACH aerosol tended to be decreased as compared to the first ACH aerosol, although the difference was not significant. The diminished effect of the agonists could be due to receptor desensibilization and/or release of adrenaline, which in turn decreases bronchoconstriction and eicosanoid release.
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PMID:Effect of histamine, acetylcholine and compound 48/80 on bronchoconstriction and release of eicosanoids in the dog. 652 15

A significant correlation between the degree of bronchial reactivity to ACH, Hi and A.E. was found in a series of 23 dogs. An increase in receptors sensitivity responsible for the organic manifestation of allergy must be assumed. This increased receptors sensitivity is an important phenomenon in asthma clinically relevant.
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PMID:The correlation between allergen, acetylcholine and histamine-induced bronchoconstriction. 653 73

Reported similarities in the acute toxic effects of 1,2-dibromo-3-chloropropane (DBCP), 3-chloro-1,2-propaneoxide (epichlorohydrin, ECH), 3-chloro-1,2-propanediol (alphachlorohydrin, ACH), and oxalic acid (OA) have been suggested as presumptive evidence that the metabolism of DBCP to OA, via ECH and ACH, is the cause of the resulting injuries to the kidney and, perhaps, to the epididymis and testis. To test this hypothesis, the comparative toxicities of these four chemicals were studied in male rats after single subcutaneous (sc) injections of maximally tolerated (nonlethal) doses. Kidney, testicular, and liver functions were monitored, and the occurrences of morphological changes in these and several other organs were evaluated 24 hr, 3, 8, 25, and 75 days post-treatment. DBCP caused renal dysfunction (alterations in urine composition and reduced glomerular filtration rate) and marked necrosis of the proximal tubular epithelium in the outer medulla of the kidney. ACH and OA also elicited renal dysfunction, but ACH produced only a mild swelling of the proximal tubular epithelium in the renal cortex and OA produced a focal necrosis anatomically associated with crystal deposition. ECH caused a swelling of the proximal tubular epithelium in the renal cortex, but not frank kidney dysfunction. DBCP also caused a reversible vacuolization of the tubular epithelium in the caput epididymis, progressive testicular atrophy, and a reduction of cauda epididymal sperm concentration. ACH and ECH produced similar effects, as well as epididymal sperm granulomas, spermatocoeles, and an increase in the number of morphologically abnormal spermatozoa. OA failed to produce discernible epididymal or testicular lesions at any time during the study. The development of similar lesions in the epididymis and testis following DBCP, ECH, or ACH treatments is consistent with the theory of metabolism of these chemicals to a common causative gonadotoxic agent. Oxalic acid (OA), however, would not appear to be the common gonadal toxicant. Differences in the effects, both morphological and functional, of DBCP, ECH, ACH, and OA on the kidney, moreover, indicate that DBCP nephropathy is not mediated through metabolism to OA and suggest, as well, that it differs causally from that induced by ECH or ACH. Therefore, the metabolism of DBCP to ECH or ACH, and of ECH or ACH to OA, is insufficient to explain totally the toxic effects of these agents on the urogenital system in male rats.
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PMID:The comparative effects of 1,2-dibromo-3-chloropropane (DBCP) and its metabolites, 3-chloro-1,2-propaneoxide (epichlorohydrin), 3-chloro-1,2-propanediol (alphachlorohydrin), and oxalic acid, on the urogenital system of male rats. 661 40

Determination of serum bile acids has long been regarded as the most sensitive indicator of liver function. An assessment was made of the clinical applicability of RIA evaluation of two of these acids, cholylglycine (CG) and sulpholithochocholyglycine (SLGG), on an empty stomach and 2hr after a cholecystokinetic meal in 109 liver patients ans 20 controls. After the meal test, both acids proved more sensitive than the usual liver function indices. Different mean values were observed for different diseases. They were in good correlation with the extent of histological damage. Values were highest in obstructive icterus, cirrhosis and neoplasia of the liver, fairly highly high in steatofibrosis, ACH and PCH, and normal in viral hepatitis in the course of resolution, aspecific reactive hepatitis, and steatosis. The meal test thus proved a good indicator of liver disease. Its wider use is to be hoped for in order that its limits and applications may be better understood.
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PMID:[Determination of serum bile acids in hepatobiliary diseases. Clinical applicability]. 670 Aug 30


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