Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacological effects of ATP and of two of its analogues, AMP-PCP and L-AMP-PCP, were investigated in various isolated smooth muscle preparations. In the guinea-pig vas deferens, the rat portal vein and the rat anococcygeus the nucleotides all caused contraction, and the order of potency was L-AMP-PCP greater than AMP-PCP greater than ATP. In the guinea-pig field-stimulated ileal longitudinal muscle the nucleotides all inhibited the contractions, and the order of potency was ATP greater than AMP-PCP greater than L-AMP-PCP. In the guinea-pig thoracic aorta ATP and AMP-PCP caused relaxations, ATP being more potent than AMP-PCP, and L-AMP-PCP caused contractions. These results are consistent with the suggestion that the ATP receptors mediating contraction of smooth muscle are different from those mediating relaxation, and show that L-AMP-PCP is a potent, specific agonist at excitatory ATP receptors.
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PMID:Pharmacological effects of L-AMP-PCP on ATP receptors in smooth muscle. 381 51

The hypothesis that the ADP-sensitive form of phosphorylated Na+, K+-ATPase contains occluded sodium ions has been tested by a procedure which involves (i) modifying the enzyme with alpha-chymotrypsin or N-ethylmaleimide (NEM) so that the ADP-sensitive form is more stable than it is in the native enzyme, (ii) phosphorylating the modified enzyme with ATP in the presence of labelled sodium ions, and (iii) forcing the phosphorylated enzyme rapidly through a cation-exchange column and measuring the labelled sodium in the effluent. The results show that ADP-sensitive phosphoenzyme prepared from alpha-chymotrypsin- or NEM-modified Na+, K+-ATPase is able to carry labelled sodium ions through a cation-exchange resin. This behaviour was not seen with native Na+, K+-ATPase or when phosphorylation was prevented by the omission of magnesium ions or by the substitution of adenylyl(beta, gamma-methylene)diphosphonate (AMP-PCP) for ATP. The occluded sodium ions were rapidly released when the phosphoenzyme was dephosphorylated by ADP. When alpha-chymotrypsin-modified enzyme was phosphorylated by ATP with 1 mM-sodium in the medium, close to three sodium ions were occluded per phospho group. The stoicheiometry at much lower sodium concentrations could not be determined satisfactorily. A consideration of the rate constants of the reactions thought to be involved in the occlusion of sodium and in the release of sodium from the occluded state shows that, so far as they are known, these constants are compatible with the hypothesis that the occluded-sodium form of the phosphoenzyme plays a central role in sodium transport through the pump.
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PMID:The occlusion of sodium ions within the mammalian sodium-potassium pump: its role in sodium transport. 608 5

The central effects of phencyclidine (PCP) were investigated using electrophysiological, biochemical, and behavioral techniques. PCP produced depressions of neuronal firing of several brain regions when applied locally or parenterally. At the cerebellar locus coeruleus Purkinje neuron pathway PCP produced depressions of spontaneous firing. Use of lesion techniques and receptor antagonists revealed that at this synapse PCP acted as an agonist, i.e., an indirect sympathomimetic in that it caused release and or blocked reuptake of norepinephrine. PCP also produce alterations in behavioral measures such as stereotypy and rotarod performance. In addition PCP, like norepinephrine, produced increases in cyclic AMP levels in cerebellar slices. Inhibition of central neuron firing, and alterations in behavior were correlated with brain and blood levels of PCP. Many effects of PCP were antagonized by neuroleptics. It can be concluded that PCP has profound effects on several indices of central neuron function and such changes can be related to the psychosis and other effects of this drug.
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PMID:Candidate mechanisms underlying phencyclidine-induced psychosis: an electrophysiological behavioral, and biochemical study. 612 73

Mouse lymphoma cells were shown to be unresponsive to prostaglandin E1 in terms of cAMP production. The endogenous ATP concentration was shown to be low. Addition of ATP in the presence of IMBX into the incubation medium resulted in elevation of the intracellular pool of ATP and the cells responded to PGE1 by increasing cAMP production. The ATP effect is specific and cannot be substituted by GTP. ATP analogue (AMP-PCP) can, however, produce a similar effect to ATP. The intracellular ATP concentration can be lowered by incubation with iodoacetate and potassium cyanide. This caused a drastic decrease of the cAMP level. Ethionine on the other hand had no effect on the intracellular ATP level.
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PMID:ATP uptake by mouse lymphoma cells. 618 Jun 74

Adenosine 5'-triphosphate (ATP), substance P (SP) and non-cholinergic nerve stimulation contracted the guinea-pig urinary bladder. SP and two poorly-degradable analogues of ATP, the enantiomers of adenylyl 5'-(beta, gamma-methylene)-diphosphonate (AMP-PCP and L-AMP-PCP), were used to desensitize the guinea-pig bladder. Desensitization of the bladder by AMP-PCP (50 microM) or by L-AMP-PCP (50 microM) abolished the responses to ATP, and inhibited the responses to non-cholinergic nerve stimulation and to SP. The responses to histamine were unaffected. Desensitization by SP (1 microM) inhibited the responses to SP itself, but not the responses to ATP, L-AMP-PCP or non-cholinergic nerve stimulation. These results suggest that SP may act partly by releasing ATP, and support the suggestion that ATP rather than SP is the non-cholinergic stimulatory transmitter.
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PMID:Desensitization of the guinea-pig urinary bladder by the enantiomers of adenylyl 5'-(beta, gamma-methylene)-diphosphonate and by substance P. 620 88

In the presence of AMP-PCP (beta, gamma-methyleneadenosine 5'-triphosphate), a non-hydrolyzable analog of ATP, negative stain images of increased morphological detail indicate that the dynein arm, attached to ciliary doublet microtubules, is composed of subunits including a cape, an elongated body and a head. The arrangement of these subunits makes it possible to distinguish A from B subfiber binding sites on a single arm and to demonstrate that the head of an extended arm on subfiber A of one ciliary doublet is capable of binding to subfiber B of an adjacent doublet in a specific orientation, which supports a key step in a current model of the mechanochemical cycle by which the arm produces microtubule sliding in the ciliary axoneme.
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PMID:Dynein arm substructure and the orientation of arm-microtubule attachments. 623 Apr 60

1. Changes in the intrinsic fluorescence of Na, K-ATPase protein have been used to monitor the interconversion of E(1) (low fluorescence) and E(2) (high fluorescence) forms of the unphosphorylated enzyme.2. In media lacking sodium and nucleotides, 1 mM-potassium was sufficient to convert practically all of the enzyme into the E(2) form. In media containing 1 mM-potassium, 1 mM-EDTA, and no sodium or magnesium, the addition of ATP, or its beta, gamma-imido or methylene analogues, converted the enzyme back into the E(1) form. The relation between nucleotide concentration and the fraction of the enzyme that was in the E(1) form could be described by a rectangular hyperbola, with a K((1/2)) of about 15 muM for ATP, 65 muM for adenylyl-imidodiphosphate (AMP-PNP) and 180 muM for adenylyl (beta, gamma-methylene)-diphosphonate (AMP-PCP). ADP also converted the enzyme back into the E(1) form, with a K((1/2)) of about 25 muM, but the relation between concentration and fraction converted was not well described by a rectangular hyperbola.3. In similar media containing 50 mM-potassium, much higher concentrations of ATP were required to convert the enzyme back into the E(1) form, and the conversion was probably incomplete.4. If we assume that ATP and potassium ions affect each other's binding solely by altering the equilibrium between E(1) and E(2) forms of the enzyme, we are able to conclude (i) that potassium ions bind to the E(1) form with a moderately low affinity, (ii) that, in the absence of nucleotides, the equilibrium between E(1)K and E(2)K is poised strongly in favour of E(2)K, (iii) that the binding of ATP to a low-affinity site alters the equilibrium constant for the interconversion of E(1)K and E(2)K by two to three orders of magnitude, so that, at saturating levels of ATP, the equilibrium is probably slightly in favour of E(1)K, and (iv) that in sodium-free, potassium-containing media, ATP will appear to bind to the enzyme more tightly than would be expected from the dissociation constant of the E(2)K. ATP complex.5. The pattern of the equilibrium constants for the various reactions between E(1), E(2), ATP and potassium is compatible with the hypothesis that the ATP-accelerated conversion of E(2)K into E(1)K, and the subsequent release of potassium ions from low-affinity inward-facing sites, are part of the normal sequence of events during potassium influx in physiological conditions.
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PMID:The equilibrium between different conformations of the unphosphorylated sodium pump: effects of ATP and of potassium ions, and their relevance to potassium transport. 624 81

When purified muscle actin was mixed with microtubule-associated proteins (MAPs) prepared from brain microtubules assembled in vitro, actin filaments were organized into discrete bundles, 26 nm in diameter. MAP-2 was the principal protein necessary for the formation of the bundles. Analysis of MAP-actin bundle formation by sedimentation and electrophoresis revealed the bundles to be composed of approximately 20% MAP-2 and 80% actin by weight. Transverse striations were observed to occur at 28-nm intervals along negatively stained MAP-actin bundles, and short projections, approximately 12 nm long and spaced at 28-nm intervals, were resolved by high-resolution metal shadowing. The formation of MAP-actin bundles was inhibited by millimolar concentrations of ATP, AMP-PCP (beta, gamma-methylene-adenosine triphosphate), and pyrophosphate but not by AMP, ADP, or GTP. The addition of ATP to a solution containing MAP-actin bundles resulted in the dissociation of the bundles into individual actin filaments; discrete particles, presumably MAP-2, were periodically attached along the splayed filaments. These results demonstrate that MAPs can bind to actin filaments and can induce the reversible formation of actin filament bundles in vitro.
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PMID:Microtubule-associated proteins (MAPs) and the organization of actin filaments in vitro. 627 Jan 55

Poliovirus replicase- and host factor-catalyzed copying of 3'-terminal polyadenylic acid [poly(A)] of poliovirion RNA was studied. Host factor-stimulated synthesis of polyuridylic acid [poly(U)] by the replicase required ATP in addition to UTP. ATP was not required for the oligouridylic acid-primed copying of 3'-terminal poly(A) of virion RNA. GTP, CTP, and AMP-PCP (5'-adenylyl beta-gamma methylenediphosphate, an ATP analog) could not replace ATP in host factor-stimulated synthesis of poly(U). Antibodies to poliovirus genome-linked protein (VPg) specifically precipitated in vitro-synthesized poly(U) from a host factor-stimulated reaction. The poly(U) synthesized in a host factor-stimulated reaction was shown to be attached to VPg precursor polypeptide(s) via a tyrosine-phosphate bond as found in poliovirion VPg-RNA.
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PMID:ATP is required for initiation of poliovirus RNA synthesis in vitro: demonstration of tyrosine-phosphate linkage between in vitro-synthesized RNA and genome-linked protein. 632 50

Adenosine 5'-triphosphate (ATP) and adenylyl 5'-(beta, gamma-methylene)-diphosphonate (AMP-PCP) both contracted the guinea-pig urinary bladder, but the response to AMP-PCP was much greater. We synthesized the enantiomer of AMP-PCP, L-adenylyl 5'-(beta, gamma-methylene)-diphosphonate (L-AMP-PCP), and tested it on the guinea-pig bladder. L-AMP-PCP contracted the guinea-pig bladder, and was more potent than AMP-PCP and much more potent than ATP. The potential breakdown product of L-AMP-PCP, L-adenosine, unlike adenosine (the breakdown product of AMP-PCP), did not inhibit contractions of the guinea-pig bladder. ATP and its enantiomer L-adenosine 5'-triphosphate (L-ATP) were rapidly degraded by the muscle, and AMP-PCP was also degraded, but more slowly. L-AMP-PCP, however, was completely resistant to degradation. L-AMP-PCP would appear to be a useful ATP analogue, as it is potent and resistant to degradation, and its potential breakdown product, L-adenosine, is inactive.
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PMID:Some pharmacological and biochemical interactions of the enantiomers of adenylyl 5'-(beta, gamma-methylene)-diphosphonate with the guinea-pig urinary bladder. 654 60


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