Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:113-59-7 (CPT)
 3,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

[D-Ala1]peptideT-amide, the linear hexapeptide H-Thr-Hse-Asn-Tyr-Thr-Asp-OH (LPT) and its cyclic analog, cyclo(-Thr-Hse-Asn-Tyr-Thr-Asp-) (CPT), were tested for their effects on the proliferation of cultured normal human keratinocytes (KTs) in comparison with vasoactive intestinal peptide (VIP). [D-Ala1]PT-NH2, LPT and VIP (all 0.1 mumol/l) increased the cell number in KT cultures, whereas CPT was ineffective. The VIP antagonist [N-Ac-Tyr1,D-Phe2]GRF (1-29)-NH2 significantly inhibited the VIP effects on KTs. On the other hand this antagonist did not affect the peptide T (PT) compounds-induced stimulation of KTs, providing indirect evidence that the mitogenic effects of VIP and PT peptides are probably mediated via different receptors.
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PMID:Effects of peptide T derivatives on the proliferation of cultured human keratinocytes. 757 55

The physiological role of oxytocin (OT) in the kidney is still unclear, although autoradiographic data have shown the existence of OT receptors in the rat kidney. We examined the effect of OT in the microperfused rabbit cortical collecting duct (CCD) by using conventional cable analysis and microscope photometry. On addition of 10(-9) M OT to the bath, the lumen-negative transepithelial voltage (VT) transiently increased and the transepithelial resistance (RT) and the fractional resistance of the apical membrane (FRA) (1st phase) both decreased. After this initial change, the lumen-negative VT gradually decreased below its baseline level and RT and FRA (second phase) both increased. These electrical changes were dose dependent and were prevented by the addition of 10(-5) M amiloride to the lumen. Although responses to OT were not prevented by 10(-9) M arginine vasopressin (AVP) or 10(-6) M of a V1-receptor antagonist (OPC-21268) or V2-receptor antagonist (OPC-31260), they were inhibited by the addition of the specific OT antagonist des-Gly-NH2-[d(CH2)3,Tyr(Me),Thr]OVT. Additional studies of intracellular free calcium ([Ca2+]i) revealed that 10(-8)-10(-6) M OT caused an increase in [Ca2+]i in CCD in a dose-dependent manner. Also, pretreatment with 2 x 10(-8) M bis-(aminophenoxy)ethane-tetraacetic acid-acetoxymethyl ester, an intracellular Ca2+ chelator, abolished the electrical and [Ca2+]i responses to OT. Pretreatment with 5 x 10(-4) M 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (CPT-cAMP) partially prevented the electrical responses to OT, thus reducing the decrease in lumen-negative VT below its basal level and the increase in RT after the 1st phase. These data show that OT affects the apical Na+ conductance of collecting duct cells through OT receptors distinct from the AVP receptors and that the effect of OT may, at least in part, be brought about by a mechanism(s) dependent on the increase in [Ca2+]i and cAMP production.
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PMID:Oxytocin affects apical sodium conductance in rabbit cortical collecting duct. 823 78

Bone remodeling requires regulated tyrosine phosphorylation mediated by specific protein tyrosine kinases, such as c-src and c-fms, and to date, unknown protein tyrosine phosphatases (PTPs). We previously reported the isolation of a novel bone-specific receptor PTP, named osteotesticular PTP (OST-PTP), which is regulated during osteoblast differentiation and after exposure to PTH. To determine the relevance of this PTH regulation, we characterized the PTH-induced increase in OST-PTP messenger RNA (mRNA) in UMR 106 cells in comparison with PTH effects on a related receptor PTP and a PTH regulated gene, rat collagenase. Treatment of cells with rat PTH 1-34 (rPTH) resulted in a dramatic concentration and time-dependent increase in OST-PTP mRNA with a threshold at 4 h (= or < 1nM rPTH) and maximal response of 6- 10-fold above control levels at 8 h (100 nM rPTH). An increase in collagenase mRNA was detectable 2 h earlier at 100 pM rPTH with a maximal response at least 5-fold greater than that observed for OST- PTP. Levels of mRNA for the structurally similar PTP, rat leucocyte antigen-related molecule, were unaffected by rPTH treatment. Administration of cycloheximide (5-100 microM) abolished the OST-PTP and collagenase responses to PTH. The cAMP analogs, CPT-cAMP (0.01-1mM; 8 h) or Sp-cAMP (0.1 and 0.5 mM) were equal or greater in their effectiveness to enhance both OST-PTP and collagenase mRNA as compared with rPTH. In contrast, phorbol esters, calcium ionophore, bovine PTH (3-34), or human PTHrP (7-34) had no effect on either transcript. Interestingly, 36 h of pretreatment of cells with epidermal growth factor (10 ng/ml), a growth factor known to modulate PTH's actions, resulted in a significant decrease in the abundance of OST-PTP mRNA after rPTH exposure. These studies suggest that regulation of OST-PTP mRNA is a secondary response to PTH stimulation that is dependent on protein synthesis and that may be primarily by activation of the protein kinase A pathway. This specific modulation of a bone receptor PTP may prove to be a critical component in the PTH modulation of osteoblast function.
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PMID:Parathyroid hormone regulates the expression of the receptor protein tyrosine phosphatase, OST-PTP, in rat osteoblast-like cells. 860 5

Smooth muscle cells isolated from the myometrium of a pregnant woman at term were infected with a replication-defective adenovirus vector expressing the E6/E7 proteins of human papilloma virus 16. A clonal line, PHM1-41, was selected by resistance to Geneticin and examined for maintenance of smooth muscle phenotype and response to oxytocin. The immortalized cell line retained morphological characteristics of proliferating smooth muscle cells in culture for up to 22 passages and has been used for over 2 years. The cells expressed smooth muscle-specific alpha-actin and retained estrogen receptors. Oxytocin receptors were present, as measured by whole cell binding assay using the oxytocin antagonist 125I-d(CH2)5[Tyr-(Me)2,Thr4,-Orn8,Tyr9-NH2] as ligand and oxytocin as competitor. The data were best described by a one-site binding model, with a Kd of 0.36 nM and a binding site concentration of 37 fmol/microgram DNA. PHM1-41 cells responded to oxytocin with an increase in intracellular free calcium (EC50 15 nM) and an increase in phosphatidylinositol turnover. Oxytocin-stimulated phosphatidylinositol turnover was inhibited by preincubation with the cAMP analog CPT-cAMP. This immortalized myometrial cell line should prove useful for studies relating to human myometrial function.
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PMID:Oxytocin-stimulated responses in a pregnant human immortalized myometrial cell line. 882 50

The influence of aniso-osmolarity on the activity of the MAP kinases Erk-1 and Erk-2 was studied in C6 glioma cells. Hypo-osmotic treatment (205 mosmol/l) led to an increased activity of Erk-1 and Erk-2 within 3 min, which became maximal at 10 min and returned to basal level within 120 min. In contrast, Erk activity was reduced under hyper-osmotic conditions (405 mosmol/l), compared to the normo-osmotic control (305 mosmol/l). Erk activation was accompanied by a mobility shift of Raf-1. Hypo-osmotic exposure increased the cytosolic Ca2+ concentration ([Ca2+]i). Absence of extracellular Ca2+ largely abolished the [Ca2+]i response to hypo-osmolarity, whereas Erk activation following hypo-osmotic stimulation remained unaffected, suggesting a Ca2+ independence of the osmosignalling pathway to the MAP kinases. Both the Ca2+ response as well as the Erk activation following hypo-osmotic exposure were maintained in the presence of the phospholipase C inhibitor U73122. Application of 8-CPT cAMP, forskolin/isobutylmethylxanthine or isoproterenol blocked Erk activation following hypo-osmotic treatment of the cells, suggesting a role of the Ras/Raf pathway upstream from Erk-1 and Erk-2. Protein kinase C (PKC) is unlikely to play a role in the hypo-osmolarity- induced signalling towards MAP kinases, as revealed by inhibition of PKC with Go6850. Inhibition of pertussis- or cholera toxin-sensitive G-proteins as well as inhibition of tyrosine kinases with genistein and of PI3 kinase by wortmannin had no effect on the Erk response to hypo-osmolarity. It is concluded that osmosignalling in C6 glioma cells differs upstream of the MAP kinases from that observed in primary rat astrocytes, H4IIE rat hepatoma cells and isolated rat hepatocytes.
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PMID:Osmosignalling in C6 glioma cells. 900 90

Na+/taurocholate (Na+/TC) cotransport in hepatocytes is mediated primarily by Na+/TC cotransporting polypeptide (Ntcp), and cyclic adenosine monophosphate (cAMP) stimulates Na+/TC cotransport by inducing translocation of Ntcp to the plasma membrane. The aim of the present study was to determine if Ntcp is a phosphoprotein and if cAMP alters Ntcp phosphorylation. Freshly prepared hepatocytes from rat livers were incubated with carrier-free 32PO4 for 2 hours, followed by incubation with 10 micromol/L 8-chlorophenylthio adenosin 3':5'-cyclic monophosphate (CPT-cAMP) for 15 minutes. Subcellular fractions isolated from 32P-labeled hepatocytes were subjected to immunoprecipitation using Ntcp antibody, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography to determine if Ntcp is phosphorylated. Ntcp immunoprecipitated from plasma membranes isolated from nonlabeled hepatocytes was subjected to immunoblot analysis using anti-phosphoserine, anti-phosphothreonine, or anti-phosphotyrosine antibody to determine whether Ntcp is a serine, threonine, or tyrosine phosphoprotein. Hepatocytes were loaded with bis-(2-amino-5-methylphenoxy)-ethane-N,N,N',N'-tetraacetic acid (MAPTA), a Ca2+ buffering agent, and the effect of CPT-cAMP on TC uptake, cytosolic [Ca2+], and ntcp phosphorylation and translocation was determined. In addition, the effect of cAMP on protein phosphatases 1 and 2A (PP1/2A) was determined in homogenates and plasma membranes obtained from CPT-cAMP-treated hepatocytes. Phosphorylation study showed that phosphorylated Ntcp is detectable in plasma membranes, and cAMP treatment resulted in dephosphorylation of Ntcp. Immunoblot analysis with phosphoamino antibodies revealed that Ntcp is a serine/threonine, and not a tyrosine, phosphoprotein, and cAMP inhibited both serine and threonine phosphorylation. In MAPTA-loaded hepatocytes, CPT-cAMP failed to stimulate TC uptake, failed to increase cytosolic [Ca2+], and failed to induce translocation and dephosphorylation of Ntcp. cAMP did not alter the activity of PP1/2A in either homogenates or in plasma membranes. Taken together, these results suggest that Ntcp is a serine/threonine phosphoprotein and is dephosphorylated by cAMP treatment. Activation of PP1/2A is not involved in cAMP-mediated dephosphorylation of Ntcp. Both translocation and dephosphorylation of Ntcp may be involved in the regulation of hepatic Na+/TC cotransport.
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PMID:Sodium taurocholate cotransporting polypeptide is a serine, threonine phosphoprotein and is dephosphorylated by cyclic adenosine monophosphate. 982 28

Recently we described a family of peptides, unrelated in sequence to IgE, that form stable beta-hairpins in solution and inhibit IgE activity in the microM range [Nakamura, G. R., Starovasnik, M. A., Reynolds, M. E. & Lowman, H. B. (2001) Biochemistry 40, 9828-9835]. Using an expanded set of peptide-phage libraries, we found a simpler motif, X(2)CPX(2)CYX, for binding to the high-affinity IgE receptor. In solution, one of these peptides spontaneously formed a covalent antiparallel dimer. We subsequently linked these monomers in a single-chain construct on phage and optimized receptor binding. Ultimately, peptides with 30 nM affinity were produced. NMR studies showed that the peptide adopts a stable fold consisting of two "zeta" (zeta)-shaped moieties. Structure-activity analyses reveal a single binding site created by the zeta-dimer, with two tyrosine residues important for structural stability and two proline residues important for Fc epsilon RI binding. The peptides inhibit histamine release from cultured cells and are extremely stable in biological fluids. The zeta peptides appear to act as competitive IgE inhibitors and suggest possibilities for design of novel IgE antagonists.
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PMID:Stable "zeta" peptides that act as potent antagonists of the high-affinity IgE receptor. 1183 Jun 61

1. The mechanisms and receptors involved in the vasoactive intestinal peptide (VIP)- and pituitary adenylate cyclase-activating polypeptide (PACAP)-induced relaxations of the pig intravesical ureter were investigated. 2. VIP, PACAP 38 and PACAP 27 concentration-dependently relaxed U46619-contracted ureteral strips with a similar potency. [Ala(11,22,28)]-VIP, a VPAC(1) agonist, showed inconsistent relaxations. 3. The neuronal voltage-gated Ca(2+) channel inhibitor, omega-conotoxin GVIA (omega-CgTX, 1 microm), reduced the VIP relaxations. Urothelium removal or blockade of capsaicin-sensitive primary afferents, nitric oxide (NO) synthase and guanylate cyclase with capsaicin (10 microm), N(G)-nitro-l-arginine (l-NOARG, 100 microm) and 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 5 microm), respectively, did not change the VIP relaxations. However, the PACAP 38 relaxations were reduced by omega-CgTX, capsaicin, l-NOARG and ODQ. 4. The VIP and VIP/PACAP receptor antagonists, [Lys(1), Pro(2,5), Arg(3,4), Tyr(6)]-VIP (1 microm) and PACAP (6-38) (0.4 microm), inhibited VIP and VIP and PACAP 38, respectively, relaxations. 5. The nonselective and large-conductance Ca(2)-activated K(+) channel blockers, tetraethylammonium (3 mm) and charybdotoxin (0.1 microm), respectively, and neuropeptide Y (0.1 microm) did not modify the VIP relaxations. The small-conductance Ca(2)-activated K(+) channel blocker apamin (1 microm) did not change the PACAP 27 relaxations. 6. The cAMP-dependent protein kinase A (PKA) blocker, 8-(4-chlorophenylthio)adenosine-3',5'-cyclic monophosphorothioate (Rp-8-CPT-cAMPS, 100 microm), reduced VIP relaxations. The phosphodiesterase 4 inhibitor rolipram and the adenylate cyclase activator forskolin relaxed ureteral preparations. The rolipram relaxations were reduced by Rp-8-CPT-cAMPS. Forskolin (30 nm) evoked a potentiation of VIP relaxations. 7. These results suggest that VIP and PACAP relax the pig ureter through smooth muscle receptors, probably of the VPAC(2) subtype, linked to a cAMP-PKA pathway. Neuronal VPAC receptors localized at motor nerves and PAC(1) receptors placed at sensory nerves and coupled to NO release, seem also to be involved in the VIP and PACAP 38 relaxations.
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PMID:Heterogeneity of neuronal and smooth muscle receptors involved in the VIP- and PACAP-induced relaxations of the pig intravesical ureter. 1466 37

To clarify the paradoxic effects of cerulenin, namely its in vitro inhibitory effects on fat catabolism and its in vivo reduction of fat mass, we studied the in vivo and in vitro effects of cerulenin on carnitine palmitoyltransferase-1 (CPT-1) activity, the rate-limiting enzyme of fatty acid oxidation. A single ip injection of cerulenin significantly reduced body weight and increased core temperature without significantly reducing food intake. In situ hybridization study revealed that a single injection of cerulenin did not affect the expression of orexigenic neuropeptide mRNA. Cerulenin's effect on CPT-1 activity was biphasic in the liver and muscle: early suppression during the first 1 h and late stimulation in the 3-5 h after ip treatment. In vitro cerulenin treatment reduced CPT-1 activity, which was overcome by cotreating with catecholamine. Intracerebroventricular injection of cerulenin increased CPT-1 activity significantly in soleus muscle, and this effect was sustained for up to 3 h. Pretreatment with alpha-methyl-p-tyrosine inhibited the cerulenin-induced increase in core temperature and the late-phase stimulating effect of cerulenin on CPT-1 activity. In adrenalectomized mice, cerulenin also increased the activity. In vivo cerulenin treatment enhanced muscle CPT-1 activity in monosodium glutamate-treated arcuate nucleus lesioned mice but not in gold thioglucose-treated ventromedial hypothalamus lesioned mice. These findings suggest that cerulenin-induced late-phase stimulating effects on CPT-1 activity and energy expenditure is mediated by the activation of innervated sympathetic nervous system neurons through the firing of undefined neurons of the ventromedial hypothalamus, rather than the arcuate nucleus.
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PMID:Carnitine palmitoyltransferase-1 (CPT-1) activity stimulation by cerulenin via sympathetic nervous system activation overrides cerulenin's peripheral effect. 1504 58

1. Phenylarsine oxide (PAO) is commonly used to inhibit tyrosine phosphatase activity. However, PAO can affect a variety of different processes because of its ability to promote sulfhydryl oxidation. In the present study, we investigated the effects that PAO has on basal and beta-adrenergically stimulated L-type Ca(2+) channel activity in isolated cardiac myocytes. 2. Extracellular application of PAO transiently stimulated the basal L-type Ca(2+) channel activity, whereas it irreversibly inhibited protein kinase A (PKA)-dependent regulation of channel activity by isoproterenol, forskolin and 8-CPT-cAMP (8-p-chlorophenylthioadenosine 3',5'-cyclic monophosphate). PAO also inhibited channel activity irreversibly stimulated in the presence of adenosine 5'-(3-thiotriphosphate) tetralithium salt. 3. Neither the stimulatory nor the inhibitory effects of PAO were affected by the tyrosine kinase inhibitor lavendustin A, suggesting that tyrosine phosphorylation is not involved. 4. Extracellular application of the sulfhydryl-reducing agent dithiothreitol (DTT) antagonized both the stimulatory and inhibitory effects of PAO. Yet, following intracellular dialysis with DTT, only the inhibitory effect of PAO was antagonized. 5. The inhibitory effect of PAO was mimicked by intracellular, but not extracellular application of the membrane impermeant thiol oxidant 5,5'-dithio-bis(2-nitrobenzoic acid). 6. These results suggest that the stimulatory effect of PAO results from oxidation of sulfhydryl residues at an extracellular site and the inhibitory effect is due to redox regulation of an intracellular site that affects the response of the channel to PKA-dependent phosphorylation. It is concluded that the redox state of the cell may play a critical role in modulating beta-adrenergic responsiveness of the L-type Ca(2+) channel in cardiac myocytes.
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PMID:Redox modulation of basal and beta-adrenergically stimulated cardiac L-type Ca(2+) channel activity by phenylarsine oxide. 1517 60


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