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:3.4.16.2 (PCP)
3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of endotoxin administration on ryanodine receptor in canine cardiac junctional sarcoplasmic reticulum (SR) were studied. The results show that the Bmax for [3H]ryanodine binding to cardiac junctional SR was decreased by 25% (8 +/- 0.38 vs 6 +/- 0.41 pmole/mg protein for control and endotoxic, respectively; (P less than 0.01) while the kd (13.7 +/- 1 nM for control vs 13.2 +/- 2 nM for endotoxic) was unaffected 4 hr following endotoxin administration. Ca2+ activated [3H]ryanodine binding in both groups sigmoidally but the Vmax for Ca2+ activation was decreased by 24% (P less than 0.05) while the S0.5 and the Hill coefficient values remained unchanged after endotoxin injection. Caffeine, ATP, and AMP-PCP activated while calmodulin, SKF-525A, ruthenium red, and Mg2+ inhibited [3H]ryanodine binding in both groups but the A0.5 (concentration requires for half-maximum activation) and the I50 (concentration requires for half-maximum inhibition) for the above-mentioned activators and inhibitors, respectively, were unaffected during endotoxin shock. Digestion of cardiac SR isolated from control dogs with phospholipase A2 inhibited [3H]ryanodine binding and the inhibition was reversed completely by the addition of phosphatidylserine. Addition of phosphatidylserine to cardiac SR isolated from endotoxic dogs stimulated [3H]ryanodine binding and the stimulation represents a complete reversal of the inhibition caused by endotoxin administration. Based on these findings together with previous observation that phospholipase A2 activity is activated during endotoxin shock, it is concluded that endotoxin administration decreases the number of ryanodine receptor in canine cardiac junctional SR and the decrease in ryanodine receptor is associated with a mechanism involving a modification of membrane lipid microenvironment in response to phospholipase A2 activation.
...
PMID:Altered ryanodine receptor of canine cardiac sarcoplasmic reticulum and its underlying mechanism in endotoxin shock. 138 10

[3H]ryanodine binding to and Ca2+ release from microsomal fractions derived from canine cerebrum (CBR) and cerebellum (CBL) were investigated. High-affinity ryanodine binding sites were detected in both cerebrum and cerebellum microsomes [CBR: maximal binding capacity (Bmax) = 446 fmol/mg protein, dissociation constant (Kd) = 9 nM, Hill coefficient (n) = 0.95; CBL: Bmax = 650, Kd = 12, n = 1.8]. Ryanodine binding in both fractions was increased by millimolar concentrations of ATP [or its nonhydrolyzable analogue beta, gamma-methyleneadenosine 5'-triphosphate (AMP-PCP)] and micromolar concentrations of Ca2+ but was decreased by micromolar concentrations of ruthenium red, similar to that found in sarcoplasmic reticulum (SR) of striated muscle. The addition of caffeine or the sudden elevation of extravesicular Ca2+ induced a rapid La(3+)-sensitive Ca2+ release from both CBR and CBL microsomal fractions with rate constants of approximately 100 s-1, as determined by stopped-flow photometry of the Ca2+ indicator arsenazo III. The release of Ca2+ was activated by either millimolar ATP or AMP-PCP, blocked by micromolar concentrations of La3+, and significantly inhibited by 50 microM ryanodine. Mg2+ and ruthenium red in millimolar and micromolar concentrations, respectively, caused only a slight inhibition of Ca2+ release. These results indicate that rapid Ca2+ release occurs from caffeine-, Ca2+- and ryanodine-sensitive Ca2+ stores in both CBR and CBL microsomal fractions.
...
PMID:Caffeine- and ryanodine-sensitive Ca2+ stores of canine cerebrum and cerebellum neurons. 172 42

A subpopulation of canine cardiac sarcoplasmic reticulum vesicles has been found to contain a "Ca2+ release channel" which mediates the release of intravesicular Ca2+ stores with rates sufficiently rapid to contribute to excitation-contraction coupling in cardiac muscle. 45Ca2+ release behavior of passively and actively loaded vesicles was determined by Millipore filtration and with the use of a rapid quench apparatus using the two Ca2+ channel inhibitors, Mg2+ and ruthenium red. At pH 7.0 and 5-20 microM external Ca2+, cardiac vesicles released half of their 45Ca2+ stores within 20 ms. Ca2+-induced Ca2+ release was inhibited by raising and lowering external Ca2+ concentration, by the addition of Mg2+, and by decreasing the pH. Calmodulin reduced the Ca2+-induced Ca2+ release rate 3-6-fold in a reaction that did not appear to involve a calmodulin-dependent protein kinase. Under various experimental conditions, ATP or the nonhydrolyzable ATP analog, adenosine 5'-(beta, gamma-methylene)triphosphate (AMP-PCP), and caffeine stimulated 45Ca2+ release 2-500-fold. Maximal release rates (t1/2 = 10 ms) were observed in media containing 10 microM Ca2+ and 5 mM AMP-PCP or 10 mM caffeine. An increased external Ca2+ concentration (greater than or equal to 1 mM) was required to optimize the 45Ca2+ efflux rate in the presence of 8 mM Mg2+ and 5 mM AMP-PCP. These results suggest that cardiac sarcoplasmic reticulum contains a ligand-gated Ca2+ channel which is activated by Ca2+, adenine nucleotide, and caffeine, and inhibited by Mg2+, H+, and calmodulin.
...
PMID:Rapid calcium release from cardiac sarcoplasmic reticulum vesicles is dependent on Ca2+ and is modulated by Mg2+, adenine nucleotide, and calmodulin. 243 95

The Ca2+-ryanodine receptor complex is a functional unit at the terminal cisternae (TC) of the sarcoplasmic reticulum (SR) whose proteins comprise the Ca2+ release channels which may be involved in excitation-contraction coupling. Ca2+, Mg2+, caffeine, and adenine nucleotides, but not inositol 1,4,5-trisphosphate, may exert their inotropic effects on skeletal muscle SR by direct allosteric modulation of the [3H]ryanodine-binding site. Micromolar Ca2+ is primarily responsible for activating [3H]ryanodine binding by regulating receptor site density, affinity, and cooperativity. Mg2+ reduces the sensitivity to Ca2+ activation by directly competing with Ca2+ for the activator site. However, inhibition by Mg2+ is overcome in the presence of beta,gamma-methyleneadenosine 5'-triphosphate (AMP-PCP; 1 mM) or caffeine (20 mM). Caffeine dramatically increases the affinity of the Ca2+ activator site for Ca2+, whereas AMP-PCP or cAMP enhances the gating efficiency or the lifetime of the open state of the TC SR channel. A kinetic model is proposed for four functional domains of the Ca2+-ryanodine receptor complex: the Ca2+-regulatory domain which binds Ca2+ with microM affinity is primarily responsible for gating the Ca2+ channel of the TC SR in a cooperative manner, and is inhibited by mM Mg2+ by direct competition for the activator site which appears to contain critical sulfhydryl groups; a Ca2+-activate alkaloid binding domain in close proximity to the channel which binds ryanodine with nM affinity and rapidly occludes upon complex formation; a domain which binds caffeine with low (greater than mM) affinity and directly influences the sensitivity of the Ca2+-regulatory site; and a domain which binds adenine nucleotides with intermediate affinity (less than mM), does not require phosphorylation, and intensifies the Ca2+ signal which triggers opening of the Ca2+-release channel.
...
PMID:Ca2+-activated ryanodine binding: mechanisms of sensitivity and intensity modulation by Mg2+, caffeine, and adenine nucleotides. 243 32

The effects of phencyclidine (PCP) on the threshold and intensity of caffeine-induced convulsions in rats were examined. There was a dose-dependent effect of PCP on convulsion intensity with significant reduction in intensity at 4.0 and 8.0 mg/kg PCP. At 16.0 mg/kg PCP, convulsant intensity was reduced in 50% of subjects but potentiated to the point of death in the remaining 50%. PCP had no significant effect on threshold for caffeine-induced convulsions. These results suggest that PCP antagonizes caffeine-induced convulsions and further suggests that the mechanisms involved in onset of caffeine-induced convulsions and the decrease of convulsion intensity are pharmacologically dissociable.
...
PMID:Phencyclidine (PCP) reduces the intensity of caffeine-induced convulsions in rats. 273 42

Five rhesus monkeys were trained to self-administer orally-delivered phencyclidine (PCP) and water under concurrent fixed-ratio (FR) 8 schedules. Liquid deliveries were contingent upon lip-contact responses on solenoid-operated drinking spouts, and food pellet delivery was contingent upon responses on a centrally-located lever. Food was available during three 1-hr periods each day under an FR 64 or FR 80 schedule. The liquids were available during three 6.5-hr periods after each food component. In the first experiment caffeine (4 or 8 mg) was added to each 6-g food pellet, and after responding stabilized, noncaffeinated pellets were substituted for the caffeinated pellets for eight days. There were no differences in food-, water- or PCP-maintained behavior due to caffeine concentration (4 vs. 8 mg/pellet) although the monkeys consumed twice as much caffeine at the higher concentration. Food-maintained responding was reliably reduced by 25-50 percent the first day of caffeine removal, and there was a recovery of responding characterized by intermittent cycles of low response rates over the next 7 days. Water and PCP intake were not systematically disrupted when caffeine access was terminated. In the second experiment the monkeys were tested with caffeinated (6 mg/pellet) and noncaffeinated pellets under conditions of PCP removal (water substitution) and reinstatement. Under both food conditions, when PCP access was terminated, pellet deliveries decreased by about 50 percent and gradually recovered over the 8-day water substitution phase. However, behavioral disruptions were more severe under conditions in which monkeys received caffeinated pellets, suggesting an interactive effect due to termination of PCP access and decreased caffeine intake. These results indicate that disruptions in operant baselines are sensitive indicators of the effects of discontinuing caffeine access; however, the severity and time course of behavioral disruptions due to caffeine removal are considerably less than after termination of PCP access.
...
PMID:Behavioral dependence on caffeine and phencyclidine in rhesus monkeys: interactive effects. 325 84

Hundreds of drugs and other substances are excreted in urine. In a comprehensive drug screen, it is impossible to identify every detectable substance. In order to delineate the most commonly detected drugs, approximately 1000 urine specimens from geographically distributed clinical laboratories were analyzed for drug substances. Twenty-nine (29) clinical laboratories submitted up to 76 consecutive urine specimens found to be positive for substances other than nicotine and caffeine. Specimens were analyzed by thin layer chromatography and special procedures for salicylates, benzoylecgonine, PCP, benzodiazepines, and cannabinoid metabolites. Every specimen was also tested for opiates, PCP, and cannabinoid metabolites by an enzyme immunoassay procedure. The total number of drugs detected in 1000 specimens was 3014, an average of three drugs per specimen; and 110 different drugs were identified. Of these, 50 drugs accounted for 95% of the total detected; 21% of the specimens contained cannabinoid metabolites, and 4% of the specimens contained cocaine and/or benzoylecgonine. Most of the specimens were routine, and only 4% originated from comatose patients.
...
PMID:Drug population in one thousand geographically distributed urine specimens. 401 Feb 36

The present study was primarily designed to explore the relationship between phencyclidine(PCP)-induced hyperactivity and the mesolimbic dopamine (DA) system. In addition, the motor-activating and behavioral effects of amphetamine (1.5 mg/kg), SKF-10,047 (25.0 mg/kg), scopolamine (1.0 mg/kg), and caffeine (10.0 mg/kg) were also measured and compared to PCP action. While all compounds produced a moderate to large degree of hyperactivity with varying time courses for effect, gross behavioral observations indicated a greater similarity between PCP and SKF-10,047 than between any of the other drugs. Following bilateral 6-hydroxydopamine lesions of the nucleus accumbens the robust locomotor-stimulating action of 5 mg/kg PCP was significantly reduced. Such lesions also successfully prevented amphetamine- and SKF-10,047-induced hyperactivity, but not the behavioral activation produced by scopolamine or caffeine. These results suggest that PCP and SKF-10,047, like amphetamine, elicit locomotor activity through presynaptic DA mechanisms within the mesolimbic system.
...
PMID:Phencyclidine-induced locomotor activity in the rat is blocked by 6-hydroxydopamine lesion of the nucleus accumbens: comparisons to other psychomotor stimulants. 614 86

Rabbit skeletal muscle sarcoplasmic reticulum was fractionated into a "Ca2+-release" and "control" fraction by differential and sucrose gradient centrifugation. External Ca2+ (2-20 microM) caused the release of 40 nmol of 45Ca2+/mg of protein/s from Ca2+-release vesicles passively loaded at pH 6.8 with an internal half-saturation Ca2+ concentration of 10-20 mM. Ca2+-induced Ca2+ release had an approximate pK value of 6.6 and was half-maximally inhibited at an external Ca2+ concentration of 2 X 10(-4) M and Mg2+ concentration of 7 X 10(-5) M. 45Ca2+ efflux from control vesicles was slightly inhibited at external Ca2+ concentrations that stimulated the rapid release of Ca2+ from Ca2+-release vesicles. Adenine, adenosine, and derived nucleotides caused stimulation of Ca2+-induced Ca2+ release in media containing a "physiological" free Mg2+ concentration of 0.6 mM. At a concentration of 1 mM, the order of effectiveness was AMP-PCP greater than cAMP approximately AMP approximately ADP greater than adenine greater than adenosine. Other nucleoside triphosphates and caffeine were minimally effective in increasing 45Ca2+ efflux from passively loaded Ca2+-release vesicles. La3+, ruthenium red, and procaine inhibited Ca2+-induced Ca2+ release. Ca2+ flux studies with actively loaded vesicles also indicated that a subpopulation of sarcoplasmic reticulum vesicles contains a Ca2+ permeation system that is activated by adenine nucleotides.
...
PMID:Adenine nucleotide stimulation of Ca2+-induced Ca2+ release in sarcoplasmic reticulum. 669 71

Groups of rats, acclimated to drinking both water and 10% v/v ethanol were implanted with a variety of slow-release devices containing d-amphetamine (d-amp), nicotine, caffeine, phencyclidine (PCP), secobarbital, LSD, mescaline or haloperidol. Ethanol intake was elevated only during treatment with d-amp or nicotine; none of the other drugs affected ethanol consumption even though the amounts of all drugs released were pharmacologically sufficient to affect behavior. Nicotine treated rats were not simply seeking calories provided by the EtOH solution, since nicotine treatment did not enhance intake of a distinctively flavored solution isocaloric to 10% ethanol. These results support a self-medication model of ethanol intake.
...
PMID:Ethanol intake increases during continuous administration of amphetamine and nicotine, but not several other drugs. 686 54


1 2 3 Next >>

---