, a bio/informatics shared resource is still "open for business" - Visit the CDS website


Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 12

Publication Record

Connections

Histamine elevates free intracellular calcium in mouse retinal dopaminergic cells via H1-receptors.
Frazão R, McMahon DG, Schunack W, Datta P, Heidelberger R, Marshak DW
(2011) Invest Ophthalmol Vis Sci 52: 3083-8
MeSH Terms: Animals, Axons, Calcium, Dopamine, Dose-Response Relationship, Drug, Histamine, Histamine Agonists, Histamine H1 Antagonists, Mice, Mice, Transgenic, Receptors, Histamine H1, Retina
Show Abstract · Added March 18, 2020
PURPOSE - Previously, retinopetal axons containing histamine and dopaminergic neurons expressing histamine H(1)-receptor had been localized in mouse retinas using anatomic techniques. The goal of these experiments was to demonstrate that these receptors are functional.
METHODS - Dopaminergic cells were acutely isolated from retinas of transgenic mice expressing red fluorescent protein under control of the tyrosine hydroxylase promoter and loaded with the calcium indicator Fura-2.
RESULTS - Under control conditions, there were spontaneous oscillations in the levels of free intracellular calcium in dopaminergic cells. These oscillations were abolished in nominally calcium-free extracellular medium and in 1 μM tetrodotoxin, findings suggesting that the oscillations were mediated by calcium entry across the plasma membrane in response to sodium-dependent action potentials. Histamine increased the mean free intracellular calcium in the dopaminergic cells by increasing the frequency and/or amplitude of the calcium oscillations. The effects of histamine were dose-dependent and reached maximum at 5 μM. With this dose, there was a 65% increase in the mean free intracellular calcium concentration. The histamine H(1)-receptor antagonist, pyrilamine, blocked the effects of 5 μM histamine when applied at 50 μM. The selective histamine H(1)-receptor agonists, 2-(3-trifluoromethylphenyl) histamine and methylhistaprodifen significantly increased mean free intracellular calcium when applied at 5 μM.
CONCLUSIONS - Histamine released from retinopetal axons in the mouse retina can elevate intracellular calcium levels in the perikarya of dopaminergic cells via the activation of histamine H(1)-receptors.
0 Communities
1 Members
0 Resources
MeSH Terms
Naringin is a major and selective clinical inhibitor of organic anion-transporting polypeptide 1A2 (OATP1A2) in grapefruit juice.
Bailey DG, Dresser GK, Leake BF, Kim RB
(2007) Clin Pharmacol Ther 81: 495-502
MeSH Terms: Adult, Anticoagulants, Beverages, Citrus paradisi, Cross-Over Studies, Data Interpretation, Statistical, Double-Blind Method, Drug Interactions, Female, Flavanones, Furocoumarins, HeLa Cells, Hesperidin, Histamine H1 Antagonists, Humans, Male, Middle Aged, Organic Anion Transporters, Reproducibility of Results, Terfenadine
Show Abstract · Added March 27, 2014
We showed previously that grapefruit and orange juices inhibited human enteric organic anion-transporting polypeptide (OATP)1A2 in vitro and lowered oral fexofenadine bioavailability clinically. Inhibition of OATP1A2 transport by flavonoids in grapefruit (naringin) and orange (hesperidin) was conducted in vitro. Two randomized, crossover, pharmacokinetic studies were performed clinically. In one study, 120 mg of fexofenadine was ingested with 300 ml grapefruit juice, an aqueous solution of naringin at the same juice concentration (1,200 microM), or water. In the other study, fexofenadine was administered with grapefruit juice, with or 2 h before aqueous suspension of the particulate fraction of juice containing known clinical inhibitors of enteric CYP3A4, but relatively low naringin concentration (34 microM), or with water. Naringin and hesperidin's half-maximal inhibitions were 3.6 and 2.7 microM, respectively. Fexofenadine area under the plasma drug concentration-time curves (AUCs) with grapefruit juice and naringin solution were 55% (P<0.001) and 75% (P<0.05) of that with water, respectively. Fexofenadine AUCs with grapefruit juice and particulate fractions were 57% (P<0.001), 96% (not significant (NS)), and 97% (NS) of that with water, respectively. Individuals tested in both studies (n=9 of 12) had highly reproducible fexofenadine AUC with water (r(2)=0.85, P<0.001) and extent of reduction of it with grapefruit juice (r(2)=0.72, P<0.01). Naringin most probably directly inhibited enteric OATP1A2 to decrease oral fexofenadine bioavailability. Inactivation of enteric CYP3A4 was probably not involved. Naringin appears to have sufficient safety, specificity, and sensitivity to be a clinical OATP1A2 inhibitor probe. Inherent OATP1A2 activity may be influenced by genetic factors. This appears to be the first report of a single dietary constituent clinically modulating drug transport.
1 Communities
1 Members
2 Resources
20 MeSH Terms
Intestinal drug transporter expression and the impact of grapefruit juice in humans.
Glaeser H, Bailey DG, Dresser GK, Gregor JC, Schwarz UI, McGrath JS, Jolicoeur E, Lee W, Leake BF, Tirona RG, Kim RB
(2007) Clin Pharmacol Ther 81: 362-70
MeSH Terms: ATP Binding Cassette Transporter, Subfamily B, Member 1, Adult, Aged, Aged, 80 and over, Beverages, Biological Availability, Blotting, Western, Carrier Proteins, Citrus paradisi, Cytochrome P-450 CYP3A, Cytochrome P-450 Enzyme System, Female, Fluorescent Antibody Technique, Food-Drug Interactions, Histamine H1 Antagonists, Humans, Immunohistochemistry, Intestinal Mucosa, Male, Middle Aged, Organic Anion Transporters, Pharmaceutical Preparations, RNA, Reverse Transcriptase Polymerase Chain Reaction, Terfenadine
Show Abstract · Added March 27, 2014
The goals of this study were to assess the extent of human intestinal drug transporter expression, determine the subcellular localization of the drug uptake transporter OATP1A2, and then to assess the effect of grapefruit juice consumption on OATP1A2 expression relative to cytochrome P450 3A4 and MDR1. Expression of drug uptake and efflux transporters was assessed using human duodenal biopsy samples. Fexofenadine uptake by different transporters was measured in a transporter-transfected cell line. We investigated the influence of grapefruit juice on pharmacokinetics of orally administered fexofenadine. The effect of grapefruit juice on the expression of intestinal transporters was determined using real-time polymerase chain reaction and Western blot analysis. In the duodenum of healthy volunteers, an array of CYP enzymes as well as uptake and efflux transporters was expressed. Importantly, uptake transporters thought to be liver-specific, such as OATP1B1 and 1B3, as well as OATP2B1 and 1A2 were expressed in the intestine. However, among OATP transporters, only OATP1A2 was capable of fexofenadine uptake when assessed in vitro. OATP1A2 colocalized with MDR1 to the brush border domain of enterocytes. Consumption of grapefruit juice concomitantly or 2 h before fexofenadine administration was associated with reduced oral fexofenadine plasma exposure, whereas intestinal expression of either OATP1A2 or MDR1 remained unaffected. In conclusion, an array of drug uptake and efflux transporters are expressed in the human intestine. OATP1A2 is likely the key intestinal uptake transporter for fexofenadine absorption whose inhibition results in the grapefruit juice effect. Although short-term grapefruit juice ingestion was associated with reduced fexofenadine availability, OATP1A2 or MDR1 expression was unaffected.
1 Communities
1 Members
2 Resources
25 MeSH Terms
Hyperadrenergic postural tachycardia syndrome in mast cell activation disorders.
Shibao C, Arzubiaga C, Roberts LJ, Raj S, Black B, Harris P, Biaggioni I
(2005) Hypertension 45: 385-90
MeSH Terms: Adrenergic beta-Antagonists, Adult, Autonomic Nervous System, Case-Control Studies, Female, Histamine H1 Antagonists, Histamine H2 Antagonists, Humans, Hypotension, Orthostatic, Mast Cells, Methyldopa, Sympatholytics, Syndrome, Tachycardia
Show Abstract · Added December 10, 2013
Postural tachycardia syndrome (POTS) is a disabling condition that commonly affects otherwise normal young females. Because these patients can present with a flushing disorder, we hypothesized that mast cell activation (MCA) can contribute to its pathogenesis. Here we describe POTS patients with MCA (MCA+POTS), diagnosed by episodes of flushing and abnormal increases in urine methylhistamine, and compared them to POTS patients with episodic flushing but normal urine methylhistamine and to normal healthy age-matched female controls. MCA+POTS patients were characterized by episodes of flushing, shortness of breath, headache, lightheadedness, excessive diuresis, and gastrointestinal symptoms such as diarrhea, nausea, and vomiting. Triggering events include long-term standing, exercise, premenstrual cycle, meals, and sexual intercourse. In addition, patients were disabled by orthostatic intolerance and a characteristic hyperadrenergic response to posture, with orthostatic tachycardia (from 79+/-4 to 114+/-6 bpm), increased systolic blood pressure on standing (from 117+/-5 to 126+/-7 mm Hg versus no change in POTS controls), increased systolic blood pressure at the end of phase II of the Valsalva maneuver (157+/-12 versus 117+/-9 in normal controls and 119+/-7 mm Hg in POTS; P=0.048), and an exaggerated phase IV blood pressure overshoot (50+/-10 versus 17+/-3 mm Hg in normal controls; P<0.05). In conclusion, MCA should be considered in patients with POTS presenting with flushing. These patients often present with a typical hyperadrenergic response, but beta-blockers should be used with great caution, if at all, and treatment directed against mast cell mediators may be required.
0 Communities
3 Members
0 Resources
14 MeSH Terms
Are herbal products dietary supplements or drugs? An important question for public safety.
Stein CM
(2002) Clin Pharmacol Ther 71: 411-3
MeSH Terms: Anti-Allergic Agents, Cardiovascular System, Ephedra, Histamine H1 Antagonists, Humans, Hypericum, Pharmacokinetics, Plant Extracts, Terfenadine, United States, United States Food and Drug Administration
Added December 10, 2013
0 Communities
1 Members
0 Resources
11 MeSH Terms
Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine.
Dresser GK, Bailey DG, Leake BF, Schwarz UI, Dawson PA, Freeman DJ, Kim RB
(2002) Clin Pharmacol Ther 71: 11-20
MeSH Terms: ATP Binding Cassette Transporter, Subfamily B, Administration, Oral, Adult, Area Under Curve, Beverages, Biological Availability, Carrier Proteins, Citrus, Double-Blind Method, Female, Flavonoids, Food-Drug Interactions, Fruit, HeLa Cells, Histamine H1 Antagonists, Humans, Intestinal Absorption, Male, Malus, Membrane Transport Proteins, Organic Anion Transporters, Organic Anion Transporters, Sodium-Dependent, Symporters, Terfenadine
Show Abstract · Added March 27, 2014
OBJECTIVES - Our objective was to examine the effect of different fruits and their constituents on P-glycoprotein and organic anion transporting polypeptide (OATP) activities in vitro and on drug disposition in humans.
METHODS - P-glycoprotein-mediated digoxin or vinblastine efflux was determined in polarized epithelial cell monolayers. OATP-mediated fexofenadine uptake was measured in a transfected cell line. The oral pharmacokinetics of 120 mg fexofenadine was assessed with water, 25%-strength grapefruit juice, or normal-strength grapefruit, orange, or apple juices (1.2 L over 3 hours) in a randomized 5-way crossover study in 10 healthy subjects.
RESULTS - Grapefruit juice and segments and apple juice at 5% of normal strength did not alter P-glycoprotein activity. Grapefruit extract reduced transport. 6',7'-Dihydroxybergamottin had modest inhibitory activity (50% inhibitory concentration [IC(50)], 33 micromol/L). In contrast, grapefruit, orange, and apple juices at 5% of normal strength markedly reduced human OATP and rat oatp activity. 6',7'-Dihydroxybergamottin potently inhibited rat oatp3 and oatp1 (IC(50), 0.28 micromol/L). Other furanocoumarins and bioflavonoids also reduced rat oatp3 activity. Grapefruit, orange, and apple juices decreased the fexofenadine area under the plasma concentration-time curve (AUC), the peak plasma drug concentration (C(max)), and the urinary excretion values to 30% to 40% of those with water, with no change in the time to reach C(max), elimination half-life, renal clearance, or urine volume in humans. Change in fexofenadine AUC with juice was variable among individuals and inversely dependent on value with water.
CONCLUSIONS - Fruit juices and constituents are more potent inhibitors of OATPs than P-glycoprotein activities, which can reduce oral drug bioavailability. Results support a new model of intestinal drug absorption and mechanism of food-drug interaction.
1 Communities
1 Members
2 Resources
24 MeSH Terms
Voltage-dependent, pertussis toxin insensitive inhibition of calcium currents by histamine in bovine adrenal chromaffin cells.
Currie KP, Fox AP
(2000) J Neurophysiol 83: 1435-42
MeSH Terms: Adenosine Triphosphate, Animals, Autocrine Communication, Calcium Channel Blockers, Calcium Channels, N-Type, Calcium Channels, Q-Type, Catecholamines, Cattle, Chelating Agents, Chromaffin Cells, Dinoprostone, Egtazic Acid, Electrophysiology, GTP-Binding Proteins, Histamine, Histamine Agonists, Histamine H1 Antagonists, Membrane Potentials, Paracrine Communication, Patch-Clamp Techniques, Pertussis Toxin, Virulence Factors, Bordetella
Show Abstract · Added March 30, 2013
Histamine is a known secretagogue in adrenal chromaffin cells. Activation of G-protein linked H(1) receptors stimulates phospholipase C, which generates inositol trisphosphate leading to release of intracellular calcium stores and stimulation of calcium influx through store operated and other channels. This calcium leads to the release of catecholamines. In chromaffin cells, the main physiological trigger for catecholamine release is calcium influx through voltage-gated calcium channels (I(Ca)). Therefore, these channels are important targets for the regulation of secretion. In particular N- and P/Q-type I(Ca) are subject to inhibition by transmitter/hormone receptor activation of heterotrimeric G-proteins. However, the direct effect of histamine on I(Ca) in chromaffin cells is unknown. This paper reports that histamine inhibited I(Ca) in cultured bovine adrenal chromaffin cells and this response was blocked by the H(1) antagonist mepyramine. With high levels of calcium buffering in the patch pipette solution (10 mM EGTA), histamine slowed the activation kinetics and inhibited the amplitude of I(Ca). A conditioning prepulse to +100 mV reversed the kinetic slowing and partially relieved the inhibition. These features are characteristic of a membrane delimited, voltage-dependent pathway which is thought to involve direct binding of G-protein betagamma subunits to the Ca channels. However, unlike virtually every other example of this type of inhibition, the response to histamine was not blocked by pretreating the cells with pertussis toxin (PTX). The voltage-dependent, PTX insensitive inhibition produced by histamine was modest compared with the PTX sensitive inhibition produced by ATP (28% vs. 53%). When histamine and ATP were applied concomitantly there was no additivity of the inhibition beyond that produced by ATP alone (even though the agonists appear to activate distinct G-proteins) suggesting that the inhibition produced by ATP is maximal. When experiments were carried out under conditions of low levels of calcium buffering in the patch pipette solution (0.1 mM EGTA), histamine inhibited I(Ca) in some cells using an entirely voltage insensitive pathway. We demonstrate that activation of PTX insensitive G-proteins (most likely Gq) by H(1) receptors inhibits I(Ca). This may represent a mechanism by which histamine exerts inhibitory (in addition to previously identified stimulatory) effects on catecholamine release.
0 Communities
1 Members
0 Resources
22 MeSH Terms
Neurotensin depolarizes cholinergic and a subset of non-cholinergic septal/diagonal band neurons by stimulating neurotensin-1 receptors.
Matthews RT
(1999) Neuroscience 94: 775-83
MeSH Terms: Action Potentials, Adamantane, Animals, Dose-Response Relationship, Drug, Female, Guinea Pigs, Histamine H1 Antagonists, Imidazoles, In Vitro Techniques, Male, Membrane Potentials, Neurons, Neurotensin, Patch-Clamp Techniques, Piperidines, Prosencephalon, Receptors, Neurotensin, Tetrodotoxin
Show Abstract · Added January 20, 2015
Identified cholinergic and a subtype of non-cholinergic, fast-firing neurons were recorded intracellularly in vitro from slices of guinea-pig brain. Recorded neurons were within the boundaries of the medial septum and vertical limb of the diagonal band of the forebrain. The effects of superfused neurotensin and neurotensin receptor antagonists were measured under single-electrode current clamp. Neurotensin consistently caused a dose-dependent, slow depolarization of cholinergic neurons that was accompanied by an increase in membrane resistance and a block of the long-duration (1-10 s) post-spike afterhyperpolarization when present. Neurotensin also blocked a shorter duration, slow afterhyperpolarization, but only in a minority of cholinergic neurons. When present, inhibition of the slow afterhyperpolarization changed the spike pattern from single spikes to short bursts. Inhibition of post-spike afterhyperpolarizations by neurotensin reversed more slowly than did other effects of neurotensin. Tetrodotoxin did not prevent the depolarizing effect of neurotensin. The non-selective neurotensin receptor antagonist, SR142948A, blocked the depolarizing effect of neurotensin but the low-affinity receptor antagonist, levocabastine, did not. A subgroup of noncholinergic, fast-firing neurons (23%) was also depolarized by neurotensin, an effect antagonized by SR142948A but not levocabastine. Neurotensin did not effect post-spike voltage transients or change the firing pattern of non-cholinergic neurons. These data suggest that neurotensin causes a slow depolarization and increased excitability of cholinergic and some noncholinergic neurons in an area of the brain that projects to the hippocampus. Neurotensin type 1 receptors appear to mediate these effects. Neurotensin may modulate hippocampal-dependent learning and memory processes through its effects on septohippocampal neurons.
0 Communities
1 Members
0 Resources
18 MeSH Terms
OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine.
Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB
(1999) Drug Metab Dispos 27: 866-71
MeSH Terms: ATP Binding Cassette Transporter, Subfamily B, Member 1, Animals, Anion Transport Proteins, Biological Transport, Active, Caco-2 Cells, Carrier Proteins, Genes, MDR, HeLa Cells, Histamine H1 Antagonists, Humans, LLC-PK1 Cells, Mice, Rats, Swine, Terfenadine, Tissue Distribution, Transfection, Vaccinia virus
Show Abstract · Added March 27, 2014
Fexofenadine, a nonsedating antihistamine, does not undergo significant metabolic biotransformation. Accordingly, it was hypothesized that uptake and efflux transporters could be importantly involved in the drug's disposition. Utilizing a recombinant vaccinia expression system, members of the organic anion transporting polypeptide family, such as the human organic anion transporting polypeptide (OATP) and rat organic anion transporting polypeptides 1 and 2 (Oatp1 and Oatp2), were found to mediate [(14)C]fexofenadine cellular uptake. On the other hand, the bile acid transporter human sodium taurocholate cotransporting polypeptide (NTCP) and the rat organic cation transporter rOCT1 did not exhibit such activity. P-glycoprotein (P-gp) was identified as a fexofenadine efflux transporter, using the LLC-PK1 cell, a polarized epithelial cell line lacking P-gp, and the derivative cell line (L-MDR1), which overexpresses P-gp. In addition, oral and i.v. administration of [(14)C]fexofenadine to mice lacking mdr1a-encoded P-gp resulted in 5- and 9-fold increases in the drug's plasma and brain levels, respectively, compared with wild-type mice. Also, a number of drug inhibitors of P-gp were found to be effective inhibitors of OATP. Because OATP transporters and P-gp colocalize in organs of importance to drug disposition such as the liver, their activity provides an explanation for the heretofore unknown mechanism(s) responsible for fexofenadine's disposition and suggests potentially similar roles in the disposition of other xenobiotics.
0 Communities
1 Members
0 Resources
18 MeSH Terms
A phase II study of vinblastine in combination with acrivastine in patients with advanced renal cell carcinoma.
Berlin J, King AC, Tutsch K, Findlay JW, Kohler P, Collier M, Clendeninn NJ, Wilding G
(1994) Invest New Drugs 12: 137-41
MeSH Terms: Adult, Aged, Carcinoma, Renal Cell, Drug Resistance, Multiple, Female, Histamine H1 Antagonists, Humans, Kidney Neoplasms, Male, Middle Aged, Neoplasm Staging, Triprolidine, Vinblastine
Show Abstract · Added March 20, 2014
Renal cell carcinoma exhibits chemoresistance attributable in part to the P-glycoprotein drug efflux mechanism. Acrivastine is a hydrophylic antihistamine that has been shown in vitro to reverse this form of resistance. After five patients were treated on a dose-finding study, seventeen patients with metastatic or unresectable renal cell carcinoma were entered into a phase II study of vinblastine in combination with acrivastine. Patients received oral acrivastine at doses of 400 mg every 4 hours for 6 days and a 96-hour continuous infusion of vinblastine at a dose of 1.6 mg/m2/24 h. Of 15 evaluable patients, no tumor responses were seen. The regimen was well-tolerated with the majority of toxicities being gastrointestinal and hematologic. Serum levels of acrivastine, its principal metabolite (270C81) and vinblastine were measured during the study. Based on in vitro data, the plasma levels of acrivastine were within a range adequate to block P-glycoprotein activity. High doses of acrivastine were well-tolerated clinically, however, the combination of acrivastine and vinblastine was not active against renal cell carcinoma.
0 Communities
1 Members
0 Resources
13 MeSH Terms