scholarly journals Evaluation of Inhibitory Effect of Recreational Drugs on Dopaminergic Terminal Neuron by PET and Whole-Body Autoradiography

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Skye Hsin-Hsien Yeh ◽  
Ming-Hsien Lin ◽  
Fan-Lin Kong ◽  
Chi-Wei Chang ◽  
Li-Chung Hwang ◽  
...  
Keyword(s):  
Specific Binding ◽  
Inhibitory Effect ◽  
Dopamine Neurons ◽  
Whole Body ◽  
Pancreatic Tumors ◽  
Recreational Drugs ◽  
Brain Disorder ◽  
Peripheral Tissues ◽  
Whole Body Autoradiography ◽  
Peripheral Organs

There is little investigation for the functional roles of peripheral dopamine. [18F]FDOPA has been used in cancer imaging (i.e., neuroendocrine and tumors pancreatic tumors) and neuroimaging (i.e., Parkinson’s disease and Huntington’s disease). Here, we accessed side effects of recreational drugs such as ketamine, cocaine, and methamphetamine on dopamine neurons in peripheral organs by using positron emission tomography (PET) imaging and quantitative whole-body autoradiography (QWBAR) with [18F]FDOPA. The images were applied for the measurement of specific binding ratios (SBRs) of striatum with the cerebellum as the reference region. Clear striatal [18F]FDOPA-derived radioactivity was observed. Moderate level of radiotracer accumulation was presented in the mucosal layers of the stomach and small intestine. The medulla layers of kidney had higher radioactivity than that of the cortex. Blocking images markedly eliminated the specific binding of [18F]FDOPA in the striatum and in peripheral organs such as stomachs, intestines, and kidney. Ketamine showed the highest inhibitory effect on striatal [18F]FDOPA-derived radioactivity followed by cocaine and methamphetamine. The current results demonstrated a useful crossing-validating tool that enhances the capability of [18F]FDOPA for further investigations of the alteration of dopaminergic neurons in the brain disorder or cancer diseases in peripheral tissues.

scholarly journals Inositol 1,3,4,5-tetrakisphosphate binding sites in neuronal and non-neuronal tissues. Properties, comparisons and potential physiological significance

1992 ◽  
Vol 288 (1) ◽  
pp. 149-154 ◽  
Author(s):  
P J Cullen ◽  
R F Irvine
Keyword(s):  
Binding Sites ◽  
Specific Binding ◽  
High Specificity ◽  
Inhibitory Effect ◽  
Scatchard Analysis ◽  
Intact Cells ◽  
Peripheral Tissues ◽  
Ligand Displacement ◽  
Neuronal Tissues ◽  
A Site

1. Ins(1,3,4,5)P4 binding sites were studied in cerebellar and hepatic microsomes from rat, and in bovine adrenal-cortical microsomes. 2. At pH 7.0, all three tissues showed specific binding, with Ins(1,3,4,5)P4 being the most potent competing ligand of those tested [which included Ins(1,4,5)P3, Ins(1,3,4,5,6)P5 and InsP6] and Scatchard analysis suggested two sites; a site with high affinity and high specificity [Kd (1-6) x 10(-9) M] and a site with low affinity and low specificity [Kd (2-6) x 10(-7) M]. 3. At pH 5.5, cerebellar and bovine adrenal microsomes showed similar binding properties: two affinities with a similar specificity for Ins(1,3,4,5)P4 as at pH 7.0. 4. However, when assayed in a low-ionic strength acetate-based buffer at pH 5.0, cerebellar microsomes retain specific Ins(1,3,4,5)P4 binding sites, whereas bovine adrenal and hepatic microsomal binding sites lose much of their specificity, as InsP6 and Ins(1,3,4,5,6)P5 are equally as potent as Ins(1,3,4,5)P4. 5. Pi (25 mM), which is frequently included in Ins(1,3,4,5)P4 binding assays, had a small inhibitory effect on binding of cerebellar and adrenal microsomes at pH 5.5, but a large effect at pH 7.0, so that a considerable decrease occurs in the amount of specific binding at pH 5.5 compared with that at pH 7.0, if Pi is omitted from the binding assay. 6. Cerebellar and adrenal microsomes were used in a ligand-displacement mass assay (conducted under near-physiological conditions, at pH 7.0) on extracts of cerebral-cortex slices stimulated with agonists, and both preparations faithfully detected the increases in Ins(1,3,4,5)P4 that occurred, implying that Ins(1,3,4,5)P4 is the principal ligand on these binding sites in intact cells. 7. Apparent contradictions in the literature with regard to Ins(1,3,4,5)P4 binding sites in neuronal and peripheral tissues can be largely accounted for by the data, and the properties of the binding sites detected at physiological pH are consistent with the possibility that they are putative receptors for the proposed second-messenger role for Ins(1,3,4,5)P4.

scholarly journals [18F]SPA-RQ/PET Study of NK1 receptors in the Whole Body of Guinea Pig and Rat

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tove J. Grönroos ◽  
Sarita Forsback ◽  
Olli Eskola ◽  
Jörgen Bergman ◽  
Päivi Marjamäki ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Specific Binding ◽  
Tracer Uptake ◽  
Whole Body ◽  
Peripheral Tissues ◽  
Nk1 Receptors ◽  
Body Distribution ◽  
Nk1 Antagonist ◽  
Substance P Antagonists ◽  
And Function

AbstractThere is a substantial interest in the development of NK1 substance P antagonists as potential treatments for various neuropsychiatric and somatic disorders. The aim of this study was to determine whether [18F]SPA-RQ can be utilized as a tool for studying the whole body distribution and function of NK1 receptors in preclinical settings. The compound was injected into guinea pigs with or without premedication with a NK1 receptor antagonist (NK1A-2). For comparison, we included two rats in the study, as the affinity of antagonists for NK1 receptors is known to vary between species. The whole body biodistribution of the tracer was determined at several time points. The tracer showed specific binding in organs compatible with the known location of NK1-receptors. Premedication with a NK1 antagonist led to an inhibited uptake of [18F]SPA-RQ in several organs of guinea pigs, notably intestine, pancreas, urinary bladder, uterus, skin and lung. Specific binding was also seen in both cortex and striatum. In contrast, negligible specific binding was observed in the rat brain with [18F]SPA-RQ, whereas the tracer uptake in peripheral tissues was similar to that seen in guinea pigs. We conclude that [18F]SPA-RQ/PET is a useful tool to study the distribution and function of peripherally located NK1 receptors e.g. in different disease models.

The Inhibitory Effect of Heparin and Related Glycosaminoglycans on Neutrophil Chemotaxis

1984 ◽  
Vol 52 (02) ◽  
pp. 134-137 ◽  
Author(s):  
Yaacov Matzner ◽  
Gerard Marx ◽  
Ruth Drexler ◽  
Amiram Eldor
Keyword(s):  
Specific Binding ◽  
Anticoagulant Activity ◽  
Neutrophil Migration ◽  
Inhibitory Effect ◽  
Chemotactic Factor ◽  
Human Neutrophils ◽  
Boyden Chamber ◽  
Neutrophil Chemotaxis ◽  
Inhibitory Effects ◽  
Chemotactic Factors

SummaryClinical observations have shown that heparin has antiinflammatory activities. The effect of heparin on neutrophil chemotaxis was evaluated in vitro in the Boyden Chamber. This method enabled differentiation between the direct effects of heparin on neutrophil migration and locomotion, and its effects on chemotactic factors. Heparin inhibited both the random migration and directed locomotion of human neutrophils toward zymosan-activated serum (ZAS) and F-met-leu-phe (FMLP). Inhibition was found to be dependent on the concentrations of the heparin and of the chemotactic factors. No specific binding of heparin to the neutrophils could be demonstrated, and heparin’s inhibitory effects were eliminated by simple washing of the cells. When added directly to the chamber containing chemotactic factor, heparin inhibited the chemotactic activity of ZAS but not that of FMLP, suggesting a direct inhibitory effect against C5a, the principal chemotactic factor in ZAS.Experiments performed with low-molecular-weight heparin, N-desulfated heparin, dextran sulfate, chondroitin sulfate and dextran indicated that the inhibitory effects of heparin on neutrophil chemotaxis are not related to its anticoagulant activity, but probably depend on the degree of sulfation of the heparin molecule.

Melatonin: a novel strategy for prevention of obesity and fat accumulation in peripheral organs through the improvements of circadian rhythms and antioxidative capacity

2020 ◽  
Vol 3 (1) ◽  
pp. 58-76 ◽  
Author(s):  
Bohan Rong ◽  
Qiong Wu ◽  
Chao Sun
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Circadian Rhythms ◽  
Regulatory Mechanisms ◽  
Antioxidative Capacity ◽  
Unicellular Alga ◽  
Peripheral Tissues ◽  
Peripheral Organs ◽  
Regulatory Effects ◽  
Novel Strategy

Melatonin is a well-known molecule for its involvement in circadian rhythm regulation and its contribution to protection against oxidative stress in organisms including unicellular alga, animals and plants. Currently, the bio-regulatory effects of melatonin on the physiology of various peripheral tissues have drawn a great attention of scientists. Although melatonin was previously defined as a neurohormone secreted from pineal gland, recently it has been identified that virtually, every cell has the capacity to synthesize melatonin and the locally generated melatonin has multiple pathophysiological functions, including regulations of obesity and metabolic syndromes. Herein, we focus on the effects of melatonin on fat deposition in various peripheral organs/tissues. The two important regulatory mechanisms related to the topic, i.e., the improvements of circadian rhythms and antioxidative capacity will be thoroughly discussed since they are linked to several biomarkers involved in obesity and energy imbalance, including metabolism and immunity. Furthermore, several other functions of melatonin which may serve to prevent or promote obesity and energy dysmetabolism-induced pathological states are also addressed. The organs of special interest include liver, pancreas, skeletal muscle, adipose tissue and the gut microbiota.

scholarly journals Hypocalcin from Stannius corpuscles inhibits gill calcium uptake in trout

1988 ◽  
Vol 254 (6) ◽  
pp. R891-R896 ◽  
Author(s):  
F. P. Lafeber ◽  
G. Flik ◽  
S. E. Wendelaar Bonga ◽  
S. F. Perry
Keyword(s):  
Rainbow Trout ◽  
Calcium Uptake ◽  
Inhibitory Effect ◽  
Whole Body ◽  
Transepithelial Potential ◽  
Low Calcium ◽  
Stannius Corpuscles ◽  
Normal Calcium

Bidirectional whole body flux and branchial Ca2+ influx were measured in freshwater rainbow trout. Intra-arterial injections of homogenates of Stannius corpuscles (CS) as well as of a 54-kDa isolated product (hypocalcin) exerted an inhibitory effect on whole body Ca2+ influx, but did not effect Ca2+ efflux. Hypocalcin was more effective in reducing Ca2+ influx in trout acclimated to low-calcium freshwater than in fish from normal-calcium water. We conclude that the isolated product (hypocalcin) represents the hypocalcemic principle of the CS. Similar doses of hypocalcin caused quantitatively similar decreases in Ca2+ influx in vivo and in the isolated perfused head preparation. This indicates that the gills form the principle target for hypocalcin in trout. The branchial transepithelial potential did not change during hormone treatments. Possible mechanisms of hypocalcin action are suggested.

scholarly journals WHOLE-BODY AUTORADIOGRAPHY OF DISTRIBUTION OF [1-14C]-2-DEOXYGLUCOSE IN MICE

1980 ◽  
Vol 13 (2) ◽  
pp. 202-210 ◽  
Author(s):  
MASAHITO WATANABE ◽  
TAKASHI KIHARA ◽  
MASAHISA SHIMADA ◽  
KIYOHISA KURIMOTO
Keyword(s):  
Whole Body ◽  
Whole Body Autoradiography

scholarly journals Desethylamiodarone antagonizes the effect of thyroid hormone at the molecular level

2001 ◽  
pp. 59-64 ◽  
Author(s):  
F Bogazzi ◽  
L Bartalena ◽  
S Brogioni ◽  
A Burelli ◽  
F Raggi ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Molecular Mechanisms ◽  
Thyroid Hormone Receptor ◽  
Molecular Level ◽  
Inhibitory Effect ◽  
Mobility Shift ◽  
Down Regulation ◽  
Nih3t3 Cells ◽  
Peripheral Tissues

OBJECTIVE: To evaluate the molecular mechanisms of the inhibitory effects of amiodarone and its active metabolite, desethylamiodarone (DEA) on thyroid hormone action. MATERIALS AND METHODS: The reporter construct ME-TRE-TK-CAT or TSHbeta-TRE-TK-CAT, containing the nucleotide sequence of the thyroid hormone response element (TRE) of either malic enzyme (ME) or TSHbeta genes, thymidine kinase (TK) and chloramphenicol acetyltransferase (CAT) was transiently transfected with RSV-TRbeta into NIH3T3 cells. Gel mobility shift assay (EMSA) was performed using labelled synthetic oligonucleotides containing the ME-TRE and in vitro translated thyroid hormone receptor (TR)beta. RESULTS: Addition of 1 micromol/l T4 or T3 to the culture medium increased the basal level of ME-TRE-TK-CAT by 4.5- and 12.5-fold respectively. Amiodarone or DEA (1 micromol/l) increased CAT activity by 1.4- and 3.4-fold respectively. Combination of DEA with T4 or T3 increased CAT activity by 9.4- and 18.9-fold respectively. These data suggested that DEA, but not amiodarone, had a synergistic effect with thyroid hormone on ME-TRE, rather than the postulated inhibitory action; we supposed that this was due to overexpression of the transfected TR into the cells. When the amount of RSV-TRbeta was reduced until it was present in a limited amount, allowing competition between thyroid hormone and the drug, addition of 1 micromol/l DEA decreased the T3-dependent expression of the reporter gene by 50%. The inhibitory effect of DEA was partially due to a reduced binding of TR to ME-TRE, as assessed by EMSA. DEA activated the TR-dependent down-regulation by the negative TSH-TRE, although at low level (35% of the down-regulation produced by T3), whereas amiodarone was ineffective. Addition of 1 micromol/l DEA to T3-containing medium reduced the T3-TR-mediated down-regulation of TSH-TRE to 55%. CONCLUSIONS: Our results demonstrate that DEA, but not amiodarone, exerts a direct, although weak, effect on genes that are regulated by thyroid hormone. High concentrations of DEA antagonize the action of T3 at the molecular level, interacting with TR and reducing its binding to TREs. This effect may contribute to the hypothyroid-like effect observed in peripheral tissues of patients receiving amiodarone treatment.

Cholecystokinin octapeptide analogues suppress food intake via central CCK-A receptors in mice

1993 ◽  
Vol 265 (3) ◽  
pp. R481-R486 ◽  
Author(s):  
Y. Hirosue ◽  
A. Inui ◽  
A. Teranishi ◽  
M. Miura ◽  
M. Nakajima ◽  
...  
Keyword(s):  
Food Intake ◽  
Receptor Antagonist ◽  
Rank Order ◽  
Peripheral Circulation ◽  
Inhibitory Effect ◽  
Peripheral Tissues ◽  
Cholecystokinin Octapeptide ◽  
The Central Nervous System ◽  
The Difference ◽  
The Brain

To examine the mechanism of the satiety-producing effect of cholecystokinin (CCK) in the central nervous system, we compared the potency of intraperitoneally (ip) or intracerebroventricularly (icv) administered CCK-8 and its analogues on food intake in fasted mice. The icv administration of a small dose of CCK-8 (0.03 nmol/brain) or of Suc-(Thr28, Leu29, MePhe33)-CCK-7 (0.001 nmol/brain) suppressed food intake for 20 min, whereas CCK-8 (1 nmol/kg, which is equivalent to 0.03 nmol/brain) or Suc-(Thr28, Leu29, MePhe33)-CCK-7 (1 nmol/kg) had satiety effect after ip administration. Dose-response studies indicated the following rank order of potency: Suc-CCK-7 > or = Suc-(Thr28, Leu29, MePhe33)-CCK-7 > or = CCK-8 > or = (Nle28,31)-CCK-8 >> desulfated CCK-8 = CCK-4 = 0 in the case of ip administration and Suc-(Thr28, Leu29, MePhe33)-CCK-7 >> Suc-CCK-7 > or = CCK-8 > or = (Nle28,31)-CCK-8 >> desulfated CCK-8 = CCK-4 = 0 in the case of icv administration. The selective CCK-A receptor antagonist MK-329 reversed the inhibitory effect of the centrally as well as peripherally administered CCK-8, or of Suc-(Thr28, Leu29, MePhe33)-CCK-7, whereas the selective CCK-B receptor antagonist L-365260 did not. The icv administered CCK-8 did not appear in the peripheral circulation. These findings suggest the participation of CCK-A receptors in the brain in mediating the satiety effect of CCK and the difference in CCK-A receptors in the brain and peripheral tissues.

Sign in / Sign up

Export Citation Format

Share Document