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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Marked differences in cardiac associated morbidity and mortality have been reported between patients with and without malnutrition. Tumor-associated cachexia may impair heart function, which further aggravate host wasting and thereby create a vicious circle. The aim of this study was to evaluate to what extent a malignant tumor may influence heart function under well-defined experimental conditions. The perfused working rat heart was used as a model. Study groups of freely-fed sarcoma-bearing rats, starved and protein-calorie malnourished (PCM) non-tumor rats were compared to freely-fed control animals. All groups of malnourished animals (tumor-bearing, starved and PCM) lost significant amounts of body and heart mass compared to freely-fed controls. Loss of heart contractile mass in tumor-bearing rats and malnourished animals did not lead to impaired heart function in any respect. The rate of oxygen uptake was significantly higher under all experimental conditions in perfused hearts from tumor-bearing rats compared with hearts from starved, PCM and freely-fed control rats. Oxygen uptake per left ventricular work was significantly higher in tumor-bearing rats but significantly lower in starved and PCM rats compared with control animals. Norepinephrine at various concentrations (10(-9)-10(-5) mol/l) in the perfusate stimulated the contractility and the left ventricular peak pressure significantly more in hearts from malnourished animals compared with that of freely-fed controls. The results show that adaptive functional changes can be recorded in the isolated perfused rat heart from sarcoma-bearing rats and after a period of comparatively acute undernutrition in non-tumor rats. A malignant tumor or the associated malnutrition does not induce impaired pumping performance despite a reduction in contractile heart mass. Increased oxygen consumption in hearts from tumor-bearing animals may contribute to elevated energy expenditure in a cancer-bearing host.
J Mol Cell Cardiol 1986 Nov
PMID:Effects of tumor-load and malnutrition on myocardial function in the isolated working rat heart. 379 77

The possible relationship between the function of nicotinic acetylcholine receptors in Lymnaea stagnalis neurons and energy metabolism was studied. Oxidative phosphorylation was activated by treatment of neurons with substrates of the tricarboxylic acid cycle and norepinephrine. Transmembrane currents induced by acetylcholine in isolated neurons were measured by voltage clamp. Succinate dehydrogenase activity was determined histochemically in the same neurons. Cyclic adenosine monophosphate concentration in ganglia were assayed by the protein saturation method of Gilman (1970). When used alone, succinate depressed the responses of about 50% of neurons to acetylcholine. Norepinephrine did not affect the acetylcholine-induced currents but almost doubled the inhibitory action of succinate. The mixture of norepinephrine and isocitrate also diminished the responses to acetylcholine but to a lesser extent than norepinephrine with succinate. A short-term exposure of the ganglia to succinate with norepinephrine led to the activation of succinate dehydrogenase in neurons and a threefold increase in cyclic adenosine monophosphate concentrations in ganglia. When used alone, norepinephrine doubled the cyclic adenosine monophosphate concentration. The results obtained suggest energy-dependent regulation of acetylcholine receptors.
Cell Mol Neurobiol 1986 Dec
PMID:Depression of neuron responses to acetylcholine by combined application of norepinephrine and substrates of the tricarboxylic acid cycle. 382 3

The results of studies on genetic control of resistance to antibiotics in Streptomyces strains are discussed. Cloning and sequence analysis of resistance genes yield information concerning their expression in homo- and heterologous systems, allow analysis of signal sequences responsible for initiation of transcription and translation. Cloning of genes coding for resistance to neomycin,viomycin, thiostrepton in Streptomyces and Bac. licheniformis ermD gene made them convenient selective markers for constructing vector molecules, useful for identification of homology regions in S. fradiae aph gene and TnS of E. coli; the site homologous to ermD gene has been thus revealed in S. erythreus chromosome. Possibilities of the studies aimed at elucidation of instability of many actinomycete characters using determinants of natural multiple resistance to antibiotics as a model are demonstrated. It has been shown that genetic instability is not related to the loss of plasmids and is associated with genes having chromosomal location. Simultaneous high frequency loss of a number of resistance characters determined by non-linked genes suggests the participation in gene activity regulation of actinomycete genome rearrangements. This is confirmed by evidence for such rearrangements found in strains with mutant phenotypes, including deletions in tyrosinase and streptomycin phosphotransferase genes in Mel- and StrS strains of S. reticuli and S. glaucescens.
Mol Gen Mikrobiol Virusol 1985 Mar
PMID:[Genetic control of Actinomycetes resistance to antibiotics]. 391 22

meta-Iodobenzylguanidine, an adrenal imaging agent used for the scintigraphic detection of human pheochromocytoma, is a substrate for the monoamine uptake system of chromaffin granules. It is accumulated by bovine chromaffin granule membrane vesicles in the presence of ATP, and it can be released by an osmotic shock. The uptake is dependent upon the generation of an H+-electrochemical gradient by an ATP-dependent H+ pump since it is blocked by an H+ ionophore and since meta-iodobenzylguanidine uptake can be driven by imposing an artificial pH gradient (inside acidic) on the membrane vesicles. The transport is saturable and its Km value (2.0 microM at pH 8.0) is similar to that of noradrenaline (5.3 microM). Transport occurs through the monoamine transporter since it is blocked by the same inhibitors, tetrabenazine and reserpine, and also by the transporter substrates noradrenaline and serotonin. Noradrenaline inhibits meta-iodobenzylguanidine uptake competitively (Ki = 13 microM). In addition, meta-iodobenzylguanidine displaces dihydrotetrabenazine and reserpine from their binding sites on chromaffin granule membranes. It is thus likely that, after in vivo administration, [131I] meta-iodobenzylguanidine is ultimately stored in chromaffin granules and that it is translocated by the monoamine transporter.
Mol Pharmacol 1986 Mar
PMID:Uptake of meta-iodobenzylguanidine by bovine chromaffin granule membranes. 395 33

The binding of receptor specific radioligands to autonomic receptors in the rat submandibular gland was characterized after chronic drug administration and surgical sympathetic denervation. Reserpine administration resulted in an up-regulation of both alpha 2-adrenergic receptors labeled by [3H]clonidine and beta 1-adrenergic receptors labeled by [3H]dihydroalprenolol. The increase in alpha 2-receptors was half-maximal 24 hr after a single injection of reserpine, and was about 10-fold greater than control after seven daily injections. By contrast, the beta-adrenergic receptor density was the same as control after 3 days of reserpine administration, but within 7 days was about 2-fold greater than control. Guanethidine or yohimbine administration also resulted in an up-regulation of alpha 2-adrenergic receptors. Reserpine administration or unilateral superior cervical ganglionectomy increased the density of alpha 1-adrenergic receptor binding sites 24-80%. Norepinephrine and methoxamine, but not clonidine, caused potassium to be released from submandibular gland slices. Prazosin, but not yohimbine, blocked this response to norepinephrine, indicating that the response was mediated by alpha 1-adrenergic receptors. Potassium release elicited by alpha 1-agonists was augmented in slices from animals that received reserpine. Neither drug treatment nor sympathetic denervation altered muscarinic cholinergic receptor binding. The densities of muscarinic and beta-adrenergic receptors were found to be 23-51% higher in glands from female rats than in glands from male rats.
Mol Pharmacol 1982 Jan
PMID:Regulation of autonomic receptors in rat submandibular gland. 612 19

In microvessels isolated from canine cerebral cortex, 32Pi is incorporated into phospholipids when incubated in physiological buffer containing [32Pi]orthophosphate. Norepinephrine (NE) selectively increases 32Pi incorporation into phosphatidylinositol (PI) and phosphatidic acid (PA) 60-200% over control levels. Half-maximal stimulation of PI labeling is observed with 1 microM NE, whereas maximal stimulation occurs at approximately 100 microM. Alpha 1-adrenergic agonists, phenylephrine and methoxamine, mimic the effects of NE, whereas isoproterenol, a beta-adrenergic receptor agonist, is ineffective. A wide variety of other agents tested had no specific effect on 32Pi incorporation into PI or PA. Prazosin, a selective alpha 1-receptor antagonist, at a concentration of 0.05 microM inhibits 50% of the stimulation due to NE (100 microM), whereas 1 microM yohimbine, an alpha 2-selective antagonist, is required to achieve the same effect. These results demonstrate the existence of an alpha 1-adrenergic receptor-mediated PI effect in isolated canine cerebral microvessels.
Mol Pharmacol 1983 Jul
PMID:An alpha1-adrenergic receptor-mediated phosphatidylinositol effect in canine cerebral microvessels. 613 51

The existence of "spare" alpha 1-adrenergic receptors in rat vas deferens was examined directly using radioligand binding assays and contractility measurements. Alpha 1-adrenergic receptors in homogenates of rat vas deferens were labeled with [125I]BE 2254 (125IBE). Norepinephrine and other full alpha 1-adrenergic receptor agonists were much less potent in inhibiting 125IBE binding than in contracting the vas deferens in vitro. Treatment with 300 nM phenoxybenzamine for 10 min to irreversibly inactivate alpha 1-adrenergic receptors caused a large decrease in the potency of full agonists in causing contraction of this tissue and a 23-48% decrease in the maximal contraction observed. Using those data, equilibrium constants for activation (Kact values) of the receptors by agonists were calculated. These Kact values agreed well with the equilibrium binding constants (KD values) determined from displacement of 125IBE binding. The reduction in alpha 1-adrenergic receptor density following phenoxybenzamine treatment was determined by Scatchard analysis of specific 125IBE binding sites and compared with the expected reduction (q values) calculated from the agonist dose-response curves before and after phenoxybenzamine treatment. Exposure to 300 nM phenoxybenzamine for 10 min resulted in a 39% decrease in specific 125IBE binding sites, which did not agree with the 93% decrease expected from the calculated q values. Treatment of vas deferens with a dose of phenoxybenzamine (10 microM for 15 min) that completely abolished the contractile response to alpha 1-adrenergic agonists caused an 82% decrease in the density of 125IBE binding sites. Tissues exposed to 300 nM phenoxybenzamine in the presence of 100 microM phentolamine or 3 microM prazosin showed no change in the dose-response curves for agonist-induced contraction or in the density of 125IBE binding sites when compared with controls. This suggests that phenoxybenzamine functionally inactivates alpha 1-adrenergic receptors at or near the receptor binding site. These experiments suggest that the potencies of agonists in activating alpha 1-adrenergic receptors in rat vas deferens agree well with their potencies in binding to the receptors. The greater potency of agonists in causing contraction may be due to spare receptors in this tissue. The data also demonstrate that phenoxybenzamine irreversibly inactivates alpha 1-adrenergic receptors in rat vas deferens, but that the decrease in receptor density is much smaller than that predicted from receptor theory.
Mol Pharmacol 1984 Jan
PMID:"Spare" alpha 1-adrenergic receptors and the potency of agonists in rat vas deferens. 614 49

Using (-)-[3H]-dihydroalprenolol ([3H]-DHA) and [3H]-norepinephrine ([3H]-NE) as probes, adrenoreceptors in mouse and rabbit adipocyte plasma membranes were studied and compared. The binding of either radioligand can be displaced by propranolol, alprenolol, isoproterenol or norepinephrine. [3H]-Norepinephrine bound to rabbit plasma membrane can be displaced by phentolamine. Based on displacement of radioligand by unlabelled stereoisomers, the binding is stereospecific for the (-) stereoisomer. Quantitative binding determinations of catecholamine radioligand as well as competitive inhibitory and displacement studies with Scatchard plots where appropriate, allowed calculation of binding parameters including Bmax and Kd for both radioligands and for the compounds listed above. Kinetics of displacement were also followed. Based on these binding parameters and kinetics, together with the activity of hormone and NaF sensitive adenylate cyclase, we conclude that both the population of beta-adrenoreceptor and its coupling efficiency for adenylate cyclase of the rabbit plasma membrane appear to be low as compared to that of mouse and rat.
Mol Cell Biochem 1981 Jan 20
PMID:Response of white adipocyte of mouse and rabbit to catecholamines and ACTH. 3. Modified binding properties of beta-adrenoreceptor and its decreased coupling efficiency for adenylate cyclase. 626 27

The interaction of agonists and antagonists with alpha 1-adrenergic receptors in rat vas deferens was examined using radioligand binding assays and contractility measurements. 125I-Labeled BE 2254 (125IBE) was found to bind rapidly and reversibly to a single class of high-affinity binding sites in homogenates of rat vas deferens. The k1 for association was 3.8 X 10(7) 1/mole-sec, the k-1 for dissociation was 2.3 X 10(-3) sec-1, and the KD was 105 pM. The order of potency for antagonists inhibiting 125IBE binding was prazosin greater than indoramin greater than phentolamine greater than yohimbine. Norepinephrine, phenylephrine, and other alpha-adrenergic agonists produced dose-dependent contractions of whole vas deferens in vitro. This contractile response was competitively inhibited by alpha-adrenergic blocking drugs with the same potency order observed for inhibition of specific 125IBE binding. Comparison of pA2 values for alpha 1- and alpha 2-selective antagonists competitively inhibiting contractile responses to norepinephrine, epinephrine, or phenylephrine suggested that these drugs caused their contractile effects solely through alpha 1-adrenergic receptors, and that there were no alpha 2-adrenergic receptors mediating contraction in this tissue. The pA2 values for antagonist inhibition of alpha-adrenergic receptor-mediated contractile responses were highly correlated (r = 0.995) with the KD values for antagonist inhibition of 125IBE binding in this tissue. The EC50 values for partial agonists were also highly correlated with the KD values for inhibition of 125IBE binding in vas deferens. However, the EC50 values of full agonists in causing contraction were in general 10- to 100-fold lower than the KD values for inhibiting 125IBE binding, possibly representing a substantial "spare receptor" population in this tissue. The results suggest that rat vas deferens contains a homogeneous population of alpha 1-adrenergic receptors mediating the contractile response to norepinephrine, that these receptors can be directly labeled with 125IBE, and that there may be a nonlinear relationship between agonist occupancy of alpha 1-adrenergic receptors and the functional response of this tissue.
Mol Pharmacol 1983 Mar
PMID:Occupancy of alpha 1-adrenergic receptors and contraction of rat vas deferens. 630 Jun 45

The binding of [2-3H]dihydrotetrabenazine (2-hydroxy-3-isobutyl-9, 10-dimethoxy-1,2,3,-4,6,7-hexahydro-11bH-benzo [a]quinolizine), a tetrabenazine derivative which binds to the catecholamine carrier of chromaffin granule membranes, has been studied as a function of the pH. The number of binding sites was constant from pH 6.5 to pH 9.0, whereas the KD decreased to a minimal plateau value, obtained at pH values higher than 7.5, the drug pKa. The pH dependency of the displacement of [3H]dihydrotetrabenazine by noradrenaline was also investigated. Noradrenaline KD values derived from displacement experiments decreased logarithmically when the pH increased from 6.5 to 8.5, i.e., for pH values lower than the pKa of noradrenaline. These pharmacological data support our previous hypothesis based on kinetic data [Scherman and Henry, Eur. J. Biochem. 116:535-539 (1981)] that the monoamine carrier of the chromaffin granule membrane binds and transports neutral amines, a form of low abundancy at physiological pH but for which it has a high affinity.
Mol Pharmacol 1983 Mar
PMID:The catecholamine carrier of bovine chromaffin granules. Form of the bound amine. 683 1


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