| 1669437 |
In vitro inhibition of stable 1,3-beta-D-glucan synthase activity from Neurospora crassa |
10.3109/14756369109069059. |
J Enzyme Inhib |
In vitro inhibition of stable 1,3-beta-D-glucan synthase activity from Neurospora crassa
Abstract
- Glucan synthase activity of Neurospora crassa was isolated by treatment of protoplast lysates with 0.1% 3-(3-cholamidopropyl)-dimethylammonio-1-propanesulfonate and 0.5% octylglucoside in 25 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffer, pH 7.4, containing 5 mM EDTA, 1 mM phenylmethylsulfonylfluoride, 200 mM inorganic phosphate, 10 microM GTP, 1 mM DTT, 10 mM sodium fluoride, and 600 mM glycerol. Resulting activity was partially purified by sucrose gradient density sedimentation. Approximately 70% of enzyme activity in the sucrose gradient peak fraction was soluble and enzyme activity was purified 7.3-fold. Partially purified enzyme activity had a half-life of several weeks at 4 degrees C, and a Km(app) of 1.66 +/- 0.28 mM. Inhibitors (Cilofungin, papulacandin B, aculeacin A, echinocandin B, sorbose and UDP) of 1,3-beta-D-glucan synthase activity were tested against crude particulate and detergent treated enzyme fractions and the Ki(app) of each inhibitor determined. It seems likely that this stable preparation of glucan synthase activity may be useful for in vitro enzyme screens for new glucan synthase inhibitors.
|
| 1672777 |
Selective activation of the B natriuretic peptide receptor by C-type natriuretic peptide (CNP). |
10.1126/science.1672777 |
Science |
Selective activation of the B natriuretic peptide receptor by C-type natriuretic peptide (CNP).
Abstract
- The natriuretic peptides are hormones that can stimulate natriuretic, diuretic, and vasorelaxant activity in vivo, presumably through the activation of two known cell surface receptor guanylyl cyclases (ANPR-A and ANPR-B). Although atrial natriuretic peptide (ANP) and, to a lesser extent, brain natriuretic peptide (BNP) are efficient activators of the ANPR-A guanylyl cyclase, neither hormone can significantly stimulate ANPR-B. A member of this hormone family, C-type natriuretic peptide (CNP), potently and selectively activated the human ANPR-B guanylyl cyclase. CNP does not increase guanosine 3',5'-monophosphate accumulation in cells expressing human ANPR-A. The affinity of CNP for ANPR-B is 50- or 500-fold higher than ANP or BNP, respectively. This ligand-receptor pair may be involved in the regulation of fluid homeostasis by the central nervous system.
|
| 1674111 |
Regional distribution of somatostatin binding sites in the human hypothalamus: a quantitative autoradiographic study |
10.1016/0306-4522(91)90123-6. |
Neuroscience |
Regional distribution of somatostatin binding sites in the human hypothalamus: a quantitative autoradiographic study
Abstract
- Using in vitro quantitative autoradiography and 125ITyr0-D-Trp8SRIF 14 as radioligand, we characterized the detailed distribution of somatostatin binding sites in human hypothalamus of both infants and adults. Guanosine triphosphate pretreatment, before incubation, allowed us to detect higher 125ITyr0-D-Trp8SRIF 14 binding site densities in hypothalamic structures such as preoptic and anterior hypothalamic areas and ventromedial and dorsomedial nuclei. In contrast, guanosine triphosphate was without effect in the other hypothalamic regions. The regional effects of guanosine triphosphate pretreatment were not different in infant and adult hypothalamus. Scatchard analysis showed that in a guanosine triphosphate-sensitive region (preoptic area) and a guanosine triphosphate-insensitive area (infundibular nucleus), 125ITyr0-D-Trp8SRIF 14 bound to a single class of binding sites. Affinities were similar in both regions, not modified by guanosine triphosphate pretreatment and not different in the adult (1.5 +/- 1.2 nM vs 3.2 +/- 2.1 nM for preoptic area and infundibular nucleus, respectively) and infant (0.9 +/- 0.5 nM vs 2.4 +/- 1.7 nM for preoptic area and infundibular nucleus). 125ITyr0-D-Trp8SRIF 14 binding sites were widely distributed in the anterior, mediobasal and posterior hypothalamus. Somatostatin 28 was twice as potent as somatostatin 14 to displace 125ITyr0-D-Trp8SRIF 14 binding in the preoptic area and infundibular nucleus. However, IC50s were 30 times lower in the preoptic area as compared with the infundibular nucleus. In adult as well as in infant, high densities were found mainly in the diagonal band of Broca, preoptic area and infundibular nucleus. Intermediate densities were localized in the anterior hypothalamic area, ventromedial, dorsomedial and lateral mammillary nuclei. The dorsal hypothalamic area, the paraventricular and medial mammillary nuclei displayed low but measurable densities. The only marked difference in the distribution of 125ITyr0-D-Trp8SRIF 14 binding sites in adult vs infant was observed in the medial and tuberal nuclei where the concentrations were seven-fold higher in adult hypothalamus.
|
| 1678504 |
Differential distribution of somatostatin receptor subtypes in rat brain revealed by newly developed somatostatin analogs |
10.1016/0306-4522(91)90351-n. |
Neuroscience |
Differential distribution of somatostatin receptor subtypes in rat brain revealed by newly developed somatostatin analogs
Abstract
- Somatostatin receptor subtypes were labeled with the somatostatin analogs 125ICGP 23996 and 125IMK 678 and the distribution of these receptors in rat brain was investigated using quantitative autoradiographic techniques. 125ICGP 23996 and 125IMK 678 specifically label different populations of somatostatin receptors in rat brain. In a number of brain regions striking differences in the distribution of the somatostatin receptor subtypes labeled by each peptide were observed. High levels of binding sites for both 125ICGP 23996 and 125IMK 678 were present in the cerebral cortex, CA1 region and subiculum of the hippocampus. In contrast, high levels of 125IMK 678 binding were found in the dentate gyrus of the hippocampus while few 125ICGP 23996 binding sites were observed in this brain region. 125ICGP 23996 binding was detected in the central region of the interpeduncular nucleus whereas the dorsal and lateral subnuclei of this brain area expressed mainly somatostatin receptors with high affinity for MK 678. The locus coeruleus and regions of the superior colliculus and hypothalamus selectively express 125IMK 678-sensitive somatostatin receptors. Furthermore, limbic structures such as the lateral septum, the nucleus accumbens and ventromedial striatum had much higher levels of 125IMK 678 binding sites than 125ICGP 23996 binding sites. Differences in the expression of the somatostatin receptor subtypes were also detected in the substantia nigra. 125ICGP 23996 binding was present in the pars reticulata but not the pars compacta whereas the reverse distribution for 125IMK 678 binding sites was observed. The differential distribution of 125ICGP 23996 and 125IMK 678 binding sites in rat brain supports the hypothesis that these peptides selectively label different somatostatin receptor subtypes in the central nervous system.
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| 1678852 |
Subtypes of brain somatostatin receptors couple to multiple cellular effector systems |
None |
Mol Pharmacol |
Subtypes of brain somatostatin receptors couple to multiple cellular effector systems
Abstract
- To investigate whether somatostatin (SRIF) receptor subpopulations mediate different physiological actions of SRIF, we tested the effects of SRIF and the SRIF agonists MK 678 and CGP 23996 on different biological responses in rat neocortical neurons in culture. Neocortical cells in culture express SRIF receptors that can be labeled with 125I-MK 678 and 125I-CGP 23996. Pharmacological analysis of the binding sites indicates that the radioligands label SRIF receptor subtypes with distinct pharmacological characteristics. These receptor subpopulations are similar to those expressed in adult rat brain. SRIF, MK 678, and CGP 23996 are able to inhibit forskolin-stimulated adenylate cyclase activity in rat neocortical membranes by 25-30%. Furthermore, they inhibit a high voltage-activated Ca2+ current in rat neocortical neurons in culture by 25-35%. Both SRIF and MK 678 potentiate a delayed rectifier K+ current in rat neocortical neurons in culture by 25-30%. In contrast, high concentrations of CGP 23996 do not alter the K+ current. In cells that do not respond to CGP 23996, MK 678 increases the delayed rectifier K+ current. The findings of these studies indicate that rat neocortical neurons in culture express functionally distinct SRIF receptor subtypes that can be differentially activated by SRIF agonists.
|
| 1679245 |
Facilitation of baroreceptor reflex response by endogenous somatostatin in the rat |
10.1016/0167-0115(91)90227-8. |
Regul Pept |
Facilitation of baroreceptor reflex response by endogenous somatostatin in the rat
Abstract
- We evaluated the potential participation of endogenous brain somatostatin-14 (SOM) in central cardiovascular regulation, using adult male Sprague-Dawley rats anesthetized with pentobarbital sodium (40 mg/kg, i.p.). Intracerebroventricular (i.c.v.) application of SOM (2 or 4 nmol) promoted a significant elevation in baroreceptor reflex (BRR) response, induced by phenylephrine (5 micrograms kg, i.v.). Blocking the endogenous SOM activity with its specific receptor antagonist, cyclo-7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(Bzl) (2 or 4 nmol, i.c.v.) or antiserum against SOM (1:20, i.c.v.), on the other hand, appreciably attenuated the same response. These modulatory effects on the BRR response were essentially duplicated upon bilateral microinjections of SOM (320 pmol), SOM antagonist (320 pmol) or anti-SOM (1:20) into the caudal portion of the nucleus of tractus solitarius (NTS), the terminal site for baroreceptor afferents. These results suggest that neurons that contain SOM may participate in cardiovascular control by tonically facilitating the BRR, possibly by exerting an influence on the neurons at the NTS.
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| 1679434 |
Azidopine noncompetitively interacts with vinblastine and cyclosporin A binding to P-glycoprotein in multidrug resistant cells |
None |
J Biol Chem |
Azidopine noncompetitively interacts with vinblastine and cyclosporin A binding to P-glycoprotein in multidrug resistant cells
Abstract
- It is believed that P-glycoprotein (P-gp) is an energy-dependent drug efflux pump responsible for decreased drug accumulation in multidrug resistant (MDR) cells. In this study, we investigated whether azidopine, a photoactive dihydropyridine calcium channel blocker, is transported by P-gp in MDR Chinese hamster lung cells, DC-3F/VCRd-5L, and whether its binding site(s) on P-gp are distinct from those of Vinca alkaloids and cyclosporins. The efflux of azidopine from MDR cells was energy-dependent and inhibited by the cytotoxic agent vinblastine (VBL). Cyclosporin A (CsA), a modulator of MDR, also increased azidopine accumulation in MDR cells by decreasing the energy-dependent efflux of azidopine. P-gp in these cells was the only protein specifically bound to 3Hazidopine in photoaffinity experiments. The specific photoaffinity labeling of P-gp by 3Hazidopine was inhibited by CsA, SDZ 33-243, nonradioactive azidopine, and VBL with median concentrations (IC50) of 0.5, 0.62, 1.7, and 25 microM, respectively. The equilibrium binding of azidopine to plasma membranes of MDR variant DC-3F/VCRd-5L cells showed a single class of specific binding sites having a dissociation constant of 1.20 microM and a maximum binding capacity of 4.47 nmol/mg of protein. Kinetic analysis indicated that the inhibitory effect of VBL and CsA on azidopine binding to plasma membranes of MDR cells was noncompetitive, indicating that azidopine binds to P-gp at a binding site(s) different from the binding site(s) of these drugs.
|
| 1680854 |
Primary structure and functional expression of the human receptor for Escherichia coli heat-stable enterotoxin. |
10.1016/s0021-9258(18)55214-5 |
J. Biol. Chem. |
Primary structure and functional expression of the human receptor for Escherichia coli heat-stable enterotoxin.
Abstract
- Heat-stable enterotoxin (STa) produced by Escherichia coli induces intestinal secretion in mammals by binding to the brush border membrane of the small intestine and activating guanylyl cyclase. We report here the cloning and expression of a cDNA encoding the human receptor for STa. The receptor contains both an extracellular ligand binding site and a cytoplasmic guanylyl cyclase catalytic domain, making it a member of the same receptor family as the natriuretic peptide receptors. Stable mammalian cell lines over-expressing the STa receptor specifically bind 125I-STa (Kd approximately 1.0 nM) and respond to STa by dramatically increasing (approximately 50-fold) cellular cGMP levels. Sequence comparisons between the human and the rat STa receptors show less conservation in the extracellular domain than similar comparisons of natriuretic peptide receptors. This divergence may indicate important species differences in ligand-receptor interaction.
|
| 1681894 |
Social recognition in male rats: age differences and modulation by MIF-I and Alaptide |
None |
Physiol Res |
Social recognition in male rats: age differences and modulation by MIF-I and Alaptide
Abstract
- Social investigatory behaviour was used as a measure of olfactory recognition in two experiments to assess social memory in adult male rats. In Experiment 1, time spent in social investigation of juvenile males by 3-month-old adults was significantly higher than time spent by 7- and 11-month-old animals. Furthermore, a reexposure to the same juvenile male 30 min after the initial exposure elicited significantly less social investigation in adult males aged 7 and 11 months but not in those aged 3 months. If the reexposure occurs 2 h later, the same juvenile is thoroughly investigated by adult males irrespective of the age. The age-related differences in social recognition are discussed in terms of the internal readiness of adult males. While the social recognition was confirmed in older adult males, it is suggested that an ability to recognize the same juvenile may be masked in young animals by a high sexual arousal. Behavioural phenomenon of the social recognition was used in Experiment 2. An administration of hypothalamic MIF-I or its synthetic derivative Alaptide to adult males 7 or 11 months old immediately after their 1st exposure to a juvenile male resulted in decreasing the time spent in social investigation of the same juvenile during a reexposure performed 120 min later. Both drugs were ineffective if adult males were reexposed to a novel juvenile. The results suggest that both MIF-I and Alaptide improved an animal's capacity to store information received through olfactory cues."
|
| 1686663 |
Disparate effects of intracisternal RX 77368 and ODT8-SS on gastric acid and serotonin release: role of adrenal catecholamines |
10.1016/0167-0115(91)90192-j. |
Regul Pept |
Disparate effects of intracisternal RX 77368 and ODT8-SS on gastric acid and serotonin release: role of adrenal catecholamines
Abstract
- Intracisternal injection of the thyrotropin releasing hormone (TRH) analogue RX 77368 (100 ng) or the somatostatin analogue ODT8-SS (1 microgram) produced an 82% and 101% increase in gastric acid secretion in 2 h pylorus-ligated rats. In contrast, dissimilar effects were produced by intracisternal injection of these peptides on the secretion of serotonin into the gastric lumen. Intracisternal RX 77368 (100 ng) produced a 496% increase in intraluminal serotonin release, while in contrast, intracisternal ODT8-SS (1 microgram) produced a 78% inhibition in intraluminal serotonin release. Bilateral adrenalectomy reversed the stimulatory effect of intracisternal RX 77368 (100 ng) on serotonin, but not acid release. The data reveal a difference in the ability of the two peptides, which act as gastric secretagogues, to produce intraluminal acid and serotonin release, and suggest that combined activation of the vagus and the adrenal gland are important in mediating basal and RX 77368-stimulated serotonin release into the gastric lumen. In particular, differential effects on adrenal catecholamine release are implicated in the divergent effects of the two peptides.
|
| 1686757 |
Physical dependence liability of dynorphin A analogs in rodents |
10.1016/0014-2999(91)90343-o. |
Eur J Pharmacol |
Physical dependence liability of dynorphin A analogs in rodents
Abstract
- To assess the physical dependence liability of dynorphin A analogs, mice were given repeated injections of various dynorphin A analogs twice daily for 5 days, and rats were given repeated administration of N-methyl-Tyr1,N-methyl-Arg7,D-Leu8dynorphin-A-(1-8) ethylamide (E-2078) twice daily for up to 7 weeks. Mice that had received repeated D-Cys2,Cys5,N-methyl-Arg7,D-Leu8dynorphin-A-(1-9) amide displayed jumping behavior after subcutaneous injection of naloxone, an opioid receptor antagonist. In contrast, the animals that had received repeated E-2078 or N-methyl-Tyr1,Phe4(p-NO2),N-methyl-Arg7,D-Leu8dynorphin-A-(1-8) ethylamide displayed very few jumps after naloxone administration. Rats that had received repeated E-2078 administration did not display withdrawal signs, such as weight loss, after either abrupt withdrawal or naloxone administration. These results indicate that E-2078 and N-methyl-Tyr1,Phe4(p-NO2),N-methyl-Arg7,D-Leu8dynorphin-A-(1-8) ethylamide may have little dependence liability and that D-Cys2,Cys5,N-methyl-Arg7,D-Leu8dynorphin-A-(1-9) amide can cause physical dependence.
|
| 1687590 |
Pharmacokinetics and brain entry of alaptide, a novel nootropic agent, in mice, rats and rabbits |
10.1111/j.2042-7158.1991.tb03200.x. |
J Pharm Pharmacol |
Pharmacokinetics and brain entry of alaptide, a novel nootropic agent, in mice, rats and rabbits
Abstract
- Pharmacokinetics of a novel nootropic agent, alaptide, have been examined in plasma and brain of mice, rats and rabbits following an intravenous dose (1 mg kg-1). First-order equilibration rate constants between plasma and brain (kBO) were calculated by a two-compartment model with a linked compartment (brain). Brain alaptide equilibrates rapidly with the central compartment in mice and rats due to the high kBO/beta ratio. In rabbits the equilibration is much slower (kBO/beta approximately 1). Partition coefficients between brain and plasma calculated from areas under the brain and plasma concentration-time curves, are 0.479, 0.549 and 0.864, in mice, rats and rabbits, respectively.
|
| 1687863 |
Effects of MIF-1 and its cyclic derivative alaptide on agonistic behaviour in mice |
None |
Homeost Health Dis |
Effects of MIF-1 and its cyclic derivative alaptide on agonistic behaviour in mice
Abstract
|
| 1687893 |
Solid phase synthesis of partially protected and free peptides containing disulphide bonds by simultaneous cysteine oxidation-release from 2-chlorotrityl resin |
10.1111/j.1399-3011.1991.tb01540.x. |
Int J Pept Protein Res |
Solid phase synthesis of partially protected and free peptides containing disulphide bonds by simultaneous cysteine oxidation-release from 2-chlorotrityl resin
Abstract
|
| 1691481 |
Febrile effects of polyriboinosinic acid: polyribocytidylic acid and interferon: relationship to somatostatin in rat hypothalamus |
10.1007/BF02583513. |
Pflugers Arch |
Febrile effects of polyriboinosinic acid: polyribocytidylic acid and interferon: relationship to somatostatin in rat hypothalamus
Abstract
- The changes in thermoregulatory effectors produced by an injection of polyriboinosinic acid: polyribocytidylic acid (Poly I:C) or interferon were assessed and compared in control rats, in rats with hypothalamic somatostatin (SS) receptor blockade and in rats with hypothalamic SS depletion. Intrahypothalamic (i.h., 0.05-0.50 microgram) or intraperitoneal (i.p., 100-600 micrograms) administration of Poly I:C caused a dose-related rise in colon temperature in control rats at all ambient temperatures (Ta) studied. A Poly I:C-induced fever was produced by increased metabolism at a Ta of 8 degrees C, whereas at 30 degrees C, it was caused by cutaneous vasoconstriction. At a Ta of 22 degrees C, the fever was caused by increased metabolism and cutaneous vasoconstriction. On the other hand, i.h. administration of SS-14 antagonist (0.1-0.5 ng) caused a dose-related fall in colon temperature at Ta of 8 degrees C or 22 degrees C. At a Ta of 8 degrees C, the hypothermia was caused by decreased metabolism, whereas at 22 degrees C, it was caused by decreased metabolism and cutaneous vasodilation. At a Ta of 30 degrees C, the thermoregulatory effectors were not affected by SS-14 antagonist treatment. Furthermore, the fever induced by Poly I:C or interferon was significantly reduced by pretreatment of rats with an i.p. dose of cysteamine (30 mg. kg-1) or an i.h. dose of SS-14 antagonist (0.1 ng). The results indicate that a somatostatinergic pathway in rat hypothalamus may mediate the fever induced by interferon or its inducer Poly I:C.
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