Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P21817 (RyR1)
 1,154 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The photoaffinity analog of ATP, 3'-O-(4-benzoyl)benzoyl-adenosine 5'-triphosphate (Bz2ATP) was used to covalently label and to identify the ATP binding site of the skeletal muscle ryanodine receptor. Like ATP, Bz2ATP stimulates up to fivefold the binding of ryanodine to its receptor. Photoactivation by ultraviolet light of the benzophenone group in the [alpha-32P]Bz2ATP results in covalent binding of [alpha-32P]Bz2ATP to the 450-kDa polypeptide, the ryanodine receptor's subunit. An apparent molar stiochiometry of Bz2ATP to the tetrameric ryanodine receptor complex of 1.146 +/- 0.087 (n = 2) was estimated. The covalent binding of [alpha-32P]Bz2ATP was inhibited by ATP and analogous compounds in the order: ATP = AdoPP[CH2]P = ADP = Ado = cAMP > AMP > ITP = GTP. Similar specificity was obtained for the stimulation of ryanodine binding by these nucleotides. ATP increased the ryanodine binding affinity by about sixfold. The polycationic dye ruthenium red, known as an inhibitor of Ca2+ release and ryanodine binding, inhibited the labeling of the ryanodine receptor by [alpha-32P]Bz2ATP. Tryptic digestion of the ryanodine receptor revealed a [alpha-32P]Bz2ATP-labeled 76-kDa tryptic fragment. Digestion of either the [alpha-32P]Bz2ATP-labeled 450-kDa or the 76-kDa polypeptides with S. aureus resulted in the appearance of four labeled fragments of 39, 33, 27 and 13 kDa, where the 39-kDa fragment is the precursor of the 27-kDa and 13-kDa fragments. The results suggest that the regulation of Ca2+ release by ATP involves an ATP binding site(s) located on the 27-kDa and 13-kDa fragments of the ryanodine receptor protein.
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PMID:Characterization and photoaffinity labeling of the ATP binding site of the ryanodine receptor from skeletal muscle. 838 21

The effects of various local anesthetics (LAs) on the skeletal muscle ryanodine receptor were tested. The LAs were divided into three categories according to their effects on the binding of ryanodine to the junctional sarcoplasmic reticulum membranes. Ryanodine binding was assayed in the presence of 0.2 M NaCl and 10 microM CaCl2. Tetracaine and dibucaine inhibit the binding with half-maximal inhibition (CI50) of 0.12 and 0.25 mM, respectively, while inhibition by benzocaine and procaine occurs with CI50 of about 10-fold higher. Lidocaine, its analogue QX-314, and prilocaine, on the other hand, stimulate the binding up to fourfold with half-maximal stimulation occurring with about 2 mM of the drugs. Lidocaine increases both the receptor affinity for ryanodine by about fivefold and the rate of ryanodine association with its binding site by about 10-fold. Tetracaine interacts with the ryanodine receptor in a non-competitive fashion with respect to ryanodine but it competes with lidocaine for its binding site, suggesting the existence of a single site for the inhibitory and stimulatory LA. The LAs also interact with the purified ryanodine receptor and produce effects similar to those with the membrane-bound receptor. Tetracaine and dibucaine inhibit binding of the photoreactive ATP analogue; [alpha-32P]benzoyl-benzoyl ATP (BzATP) to the ATP regulatory site of the ryanodine receptor, and high concentrations of ATP decrease the degree of ryanodine binding inhibition by tetracaine, indicating the relationship between the receptor conformations stabilized by ATP and LAs. Based on a structure-activity relationship, a model for the LA site of interaction in the ryanodine receptor is suggested.
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PMID:The interaction of local anesthetics with the ryanodine receptor of the sarcoplasmic reticulum. 839 May 76

The distributions of ryanodine receptor-like immunoreactivity and Ca-ATPase-like immunoreactivity were identified in the guinea-pig and rat central nervous system using antibodies raised against the rabbit skeletal muscle ryanodine receptor and Ca-ATPase. In both guinea-pig and rat cerebellum, the ryanodine receptor-like immunoreactivity was restricted to the soma and dendrites of Purkinje cells. In the medulla, neuron somata in the hypoglossal nucleus were stained in both species, but in the dorsal motor nucleus of the vagus somata were stained in guinea-pigs but not in rats. This species difference in ryanodine receptor-like immunoreactivity is consistent with the species difference in expression of a ryanodine sensitive, calcium activated potassium conductance in neurons of the dorsal motor nucleus of the vagus. Immunoreactivity to Ca-ATPase was present in vagal motoneurons in both species with denser staining in the guinea-pig. The data further support the idea that, in neurons of the dorsal motor nucleus of the vagus, release of intracellular calcium stores via a ryanodine receptor activates a specific class of potassium channels, thereby modulating cell excitability.
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PMID:Distribution of ryanodine receptor-like immunoreactivity in mammalian central nervous system is consistent with its role in calcium-induced calcium release. 839 Jun 24

Pietrain swine homozygous for the hal gene (n) associated with porcine stress syndrome (PSS) and a Pietrain-derivative breed, Near Pietrain (NP), with a frequency of .31 for n, were mated to produce reciprocal F1, F2, and purebred NP litters. The halothane challenge test was performed on all 40 parents and 240 progeny to predict their hal genotype and PSS susceptibility. The DNA-based assay for a C to T mutation at base pair 1,843 of the skeletal muscle ryanodine receptor (ryr1) cDNA, which is very highly correlated with PSS, was also determined for these animals. The predicted hal genotypes observed in the progeny differed significantly from the expected Mendelian ratios, and the halothane challenge test consistently overestimated the n/n hal genotype. However, the ryr1 genotypes observed in the progeny did not differ significantly from the expected Mendelian ratios, and this DNA-based assay apparently misidentified only one of the 40 parents. The results of this study indicate that the assay for the ryr1 mutation more accurately predicts both the homozygous and heterozygous forms of the PSS gene than does the halothane challenge test.
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PMID:Relative accuracy of the halothane challenge test and a molecular genetic test in detecting the gene for porcine stress syndrome. 839 44

Two novel natural ryanoids from extracts of the wood of Ryania speciosa Vahl were evaluated with sarcoplasmic reticulum (SR) vesicles for their binding affinities and their activating and deactivating effects on Ca2+ release channels. The new ryanoids, which are more polar than the known Ryania constituents ryanodine and didehydro-(9,21)-ryanodine, were purified using silica gel column chromatography and reverse phase high performance liquid chromatography. The new ryanoids were designated ester E and ester F, in keeping with nomenclature previously used in the literature. These compounds were identified by NMR spectroscopy and mass spectroscopy as C9ax-hydroxyryanodine and C8ax-hydroxy-C10-epi-dehydroryanodine, respectively. Binding of esters E and F to the high affinity (nanomolar Kd) site on SR Ca2+ release channels was determined from relative binding affinity assays using 6.7 nM [3H]ryanodine. Apparent Kd values of ryanodine, ester E, and ester F for binding to this domain on the skeletal muscle ryanodine receptor/SR Ca2+ release channel were 4.4 +/- 0.8, 65 +/- 10, and 257 +/- 53 nM, respectively (mean +/- standard deviation, four or more experiments). Apparent Kd values for cardiac muscle receptors were 0.51 +/- 0.01, 12 +/- 0.4, and 57 nM, respectively. As a functional indication of the effects of the ryanoids, channel-opening (activator) and channel-closing (deactivator) actions were assessed from the ability of the ryanoids to alter the rate of Ca2+ efflux from passively loaded skeletal muscle junctional sarcoplasmic reticular vesicles (JSRV). Activator actions among the ryanoids were similar, in that they exhibited apparently parallel concentration-effect curves, having a slope of 40% Ca2+ loss/decade increment in ryanoid concentration. Half-maximal values for activation (EC50 values) were 2.5, 63, and 43 microM for ryanodine, ester E, and ester F, respectively. Maximal channel opening by ester E was significantly less than that produced by the other ryanoids. The deactivator actions of the compounds on skeletal JSRV were dissimilar, in that their concentration-effect curves appeared not to be parallel. The quotient of the EC50 for deactivation and that for activation was taken as the concentration-coupling ratio (CCR). The CCR for ryanodine was 114 and that for ester F was 72, but the CCR for ester E was only 21. ATP-dependent Ca2+ accumulation by cardiac JSRV provided a second means to evaluate deactivator actions of the ryanoids. Results from cardiac JSRV assays were in general similar to those from skeletal JSRV assays.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Differential activating and deactivating effects of natural ryanodine congeners on the calcium release channel of sarcoplasmic reticulum: evidence for separation of effects at functionally distinct sites. 839 96

Intermittent noise occurring during sleep has been found to induce heart rate, peripheral vasomotor and electroencephalogram (EEG) changes. This study analysed these responses during the daytime and night-time sleep of shiftworkers doing a three shift system, to determine the influence of the inversion of the sleep-wake cycle on the sensitivity to noise. A group of 14 shiftworkers [aged 37 (SD 5) years] underwent an habituation daytime sleep, two experimental daytime sleeps and a night-time sleep. Traffic noises were presented during sleep [truck, 71 dB(A); motorbike, 67 dB(A); and car, 64 dB(A)] at a rate of nine each hour. The EEG measurements of sleep, electrocardiogram and finger pulse amplitude were recorded continuously. The results were expressed by computing the percentage of observed cardiac response (%HRR) and vasoconstrictive response (%FPR), magnitude of heart rate variation (heart rate response; HRR), percentage of reduction of the digital blood flow (finger pulse response, FPR), cardiac cost (CC = % HRR x HRR) and vasomotor cost (VC = % FPR x FPR). The results showed that, compared to night-time sleep, there was change in the structure of daytime sleep, that is an increase in slow wave sleep (SWS), especially stage 4 sleep decrease of stage 2 and rapid eye movement (REM) sleep latencies, and an earlier SWS and REM sleep barycentric point. During daytime sleep the % FPR was significantly smaller in SWS than in stage 2 or REM sleep. Large differences were observed in % HRR, HRR and CC between daytime sleep stages (SWS less than stage 2 less than REM sleep).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Electroencephalogram and cardiovascular responses to noise during daytime sleep in shiftworkers. 842 16

Porcine skeletal and cardiac muscle sarcoplasmic reticulum (SR) vesicle fractions enriched in the ryanodine receptor were phosphorylated in the presence of [gamma-32P]MgATP and either exogenous cAMP-dependent protein kinase (cAMP-PK), or Ca2+ plus calmodulin. Phosphorylation of the cardiac muscle ryanodine receptor in the presence of either cAMP-PK or calmodulin (6.4 and 10.6 pmol Pi/mg SR respectively) was approximately equal to or twice the [3H]ryanodine binding activity of this preparation (5.2 pmol/mg). Furthermore, cardiac muscle ryanodine receptor Pi incorporation catalyzed by cAMP-PK and calmodulin was approximately additive. In skeletal muscle SR, however, the level of cAMP-PK or calmodulin catalyzed phosphorylation of the intact ryanodine receptor (0.2 or 2.9 pmol Pi/mg SR, respectively) was much less than the [3H]ryanodine binding activity of this fraction (11.6 pmol/mg). Furthermore, Pi incorporation into the intact skeletal muscle ryanodine receptor was 3-8-fold less than that incorporated into a component of slightly lower M(r). Although this latter component comigrated with an immunoreactive fragment of the ryanodine receptor on polyacrylamide gels, it did not appear to be derived from the ryanodine receptor. We conclude that the significant phosphorylation of the cardiac muscle SR ryanodine receptor indicates a likely physiological role for protein kinase-mediated regulation of this Ca(2+)-channel. In contrast, the minimal phosphorylation of the skeletal muscle SR ryanodine receptor indicates that such a role of protein kinases is unlikely in this tissue.
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PMID:Phosphorylation of the porcine skeletal and cardiac muscle sarcoplasmic reticulum ryanodine receptor. 843 48

The AO-HRR pseudoisochromatic plates are commonly used for color vision testing in pediatric ophthalmology; however, the recommended procedure for obtaining proper illumination (a completely darkened room and standard illuminant) is typically not followed. To evaluate the role of the illuminant in clinical testing with the AO-HRR, 132 children, ages 3 to 16 years, were tested with and without the recommended illuminant (MacBeth Easel Lamp) and with the self-illuminated APT-5 Color Vision Tester. Twenty-two failed the AO-HRR with the recommended illuminant; 28 failed the AO-HRR without the illuminant. Only 13 failed the APT-5. The Cochran Q test for three related samples showed that the differences among the three groups were significant (Q = 17.1, P < .001). Diagnostic evaluation following clinical screening indicated that the differences among the tests were primarily due to false alarms, which were greatest without the recommended illuminant and least with the APT-5. These results demonstrate the importance of controlled illumination in color vision testing, either by using the recommended illumination with the AO-HRR or a self-illuminated test such as the APT-5.
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PMID:The importance of controlled illumination in color vision testing in a pediatric ophthalmology clinical practice. 845 24

This study sought to evaluate the prognostic value of clinical and laboratory parameters on survival in human immunodeficiency virus (HIV) seropositive and HIV seronegative patients with extrapulmonary tuberculosis (TB) from Tanzania. Over an 8-month period 192 consecutive patients with extrapulmonary TB, admitted to a major referral center in Tanzania, were enrolled in the study. Their symptoms, signs, and PPD skin test results were noted. Their sera were tested for HIV and analyzed for beta-2-microglobulin content. Univariate risk factors for 12 months' survival after the start of anti-TB chemotherapy were entered into a stepwise Cox regression model. Survival probabilities were estimated according to the number of risk factors. Of the 192 patients, 126 (65.6%) were HIV-infected, and 29.7% had disseminated TB. 35 patients, of whom 24 (68.6%) were HIV-positive, withdrew from the study immediately after hospital discharge. For survival analysis 157 patients remained. Within 12 months' follow-up after initiation of anti-TB therapy, the case fatality rate of the 102 HIV-infected patients was 22% and of the 55 HIV seronegative patients 2% (p 0.001). In the HIV seropositive patients the following independent risk factors were significantly associated with a decreased probability of survival: peripheral lymphadenopathy (Hazard Rate Ratio [HRR] 5.2, 95% confidence interval [CI] 1.7-16.2), a decreased activity score (bedridden 50%/day) (HRR 4.5, 95% CI 1.7-11.7), lymphopenia of 1000/mcl (HRR 4.4, 95% CI 1.7-11.8), and mycobacteremia (HRR 4.0, 95% CI 1.2-13.1). An anergic PPD skin test reaction proved to be another independent risk factor when the analysis was performed on 89 patients with available Mantoux test results. In the HIV seropositive patients, the 12 months' survival probabilities were 93%, 86%, 54%, and 0% for the presence of 0, 1, 2, and 2 risk factors respectively. The conclusion is that estimation of survival probabilities in patients with extrapulmonary TB may be possible without performing CD4 cell counts. (author's modified)
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PMID:Predictive markers of survival in HIV-seropositive and HIV-seronegative Tanzanian patients with extrapulmonary tuberculosis. 859 71

Two structurally related forms of intracellular calcium release channels that can mediate the release of intracellular calcium have been identified: the ryanodine receptors (RyR) and the inositol 1,4,5-trisphosphate receptors (IP3R). Each channel responds to distinct pathways for activation. The IP3R is activated by IP3 and the RyR is thought to be activated by calcium or by another second messenger cADP ribose. It has been proposed that each type of channel subserves a specialized pool of intracellular calcium, and it is not understood why some cell types require more than one form of intracellular calcium release channel. The present study was designed to examine whether the RyR can substitute for the IP3R during oocyte maturation. IP3R expression was inhibited in Xenopus laevis oocytes using antisense oligonucleotides. These oocytes, with reduced levels of IP3R, demonstrated a marked delay in the time course of progesterone-induced maturation. The cloned skeletal muscle RyR1 was then expressed in X. laevis oocytes that were deficient in IP3R. Functional studies showed that the properties of the cloned RyR1, expressed in oocytes, were comparable to those of the native RyR1. X. laevis oocytes deficient in IP3R, but expressing RyR1, were able to undergo progesterone-induced maturation with a time course comparable to that seen in wild-type oocytes when caffeine was used to activate RyR and induce intracellular calcium release. These studies show that RyR1 can substitute for the IP3R as the intracellular calcium release channel required for Xenopus oocyte maturation and that intracellular calcium release is important for controlling the rate of progesterone-induced maturation.
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PMID:Expressed ryanodine receptor can substitute for the inositol 1,4,5-trisphosphate receptor in Xenopus laevis oocytes during progesterone-induced maturation. 861 69


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