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Pharmaceuticals, Volume 4, Issue 4 (April 2011) – 6 articles , Pages 567-680

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Research

Jump to: Review

279 KiB  
Article
Analysis of Indonesian Spice Essential Oil Compounds That Inhibit Locomotor Activity in Mice
by Muchtaridi, Adjeng Diantini and Anas Subarnas
Pharmaceuticals 2011, 4(4), 590-602; https://doi.org/10.3390/ph4040590 - 06 Apr 2011
Cited by 19 | Viewed by 7937
Abstract
Some fragrance components of spices used for cooking are known to have an effect on human behavior. The aim of this investigation was to examine the effect of the essential oils of basil (Ocimum formacitratum L.) leaves, lemongrass (Cymbopogon citrates L.) [...] Read more.
Some fragrance components of spices used for cooking are known to have an effect on human behavior. The aim of this investigation was to examine the effect of the essential oils of basil (Ocimum formacitratum L.) leaves, lemongrass (Cymbopogon citrates L.) herbs, ki lemo (Litsea cubeba L.) bark, and laja gowah (Alpinia malaccencis Roxb.) rhizomes on locomotor activity in mice and identify the active component(s) that might be responsible for the activity. The effect of the essential oils was studied by a wheel cage method and the active compounds of the essential oils were identified by GC/MS analysis. The essential oils were administered by inhalation at doses of 0.1, 0.3, and 0.5 mL/cage. The results showed that the four essential oils had inhibitory effects on locomotor activity in mice. Inhalation of the essential oils of basil leaves, lemongrass herbs, ki lemo bark, and laja gowah rhizomes showed the highest inhibitory activity at doses of 0.5 (57.64%), 0.1 (55.72%), 0.5 (60.75%), and 0.1 mL/cage (47.09%), respectively. The major volatile compounds 1,8-cineole, α-terpineol, 4-terpineol, citronelol, citronelal, and methyl cinnamate were identified in blood plasma of mice after inhalation of the four oils. These compounds had a significant inhibitory effect on locomotion after inhalation. The volatile compounds of essential oils identified in the blood plasma may correlate with the locomotor-inhibiting properties of the oil when administered by inhalation. Full article
(This article belongs to the Special Issue Bioactive Compounds)
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511 KiB  
Article
The Role of Phosphatidylinositol-3-Kinase and AMP-Activated Kinase in the Rapid Estrogenic Attenuation of Cannabinoid-Induced Changes in Energy Homeostasis
by Garrett S. Jeffery, Kelly C. Peng and Edward J. Wagner
Pharmaceuticals 2011, 4(4), 630-651; https://doi.org/10.3390/ph4040630 - 12 Apr 2011
Cited by 12 | Viewed by 7219
Abstract
We sought to determine the involvement of phosphatidyl inositol 3-kinase (PI3K) and AMP-activated protein kinase (AMPK) in the estrogenic antagonism of the cannabinoid regulation of energy homeostasis. Food intake and body weight were evaluated in ovariectomized female guinea pigs treated s.c. with estradiol [...] Read more.
We sought to determine the involvement of phosphatidyl inositol 3-kinase (PI3K) and AMP-activated protein kinase (AMPK) in the estrogenic antagonism of the cannabinoid regulation of energy homeostasis. Food intake and body weight were evaluated in ovariectomized female guinea pigs treated s.c. with estradiol benzoate (EB) or its sesame oil vehicle, or the CB1 receptor antagonist AM251 or its cremephor/ethanol/0.9% saline vehicle. AMPK catalytic subunit, PI3K p85α regulatory subunit and proopiomelanocortin (POMC) gene expression was assessed via quantitative RT-PCR in microdissected hypothalamic tissue. Whole-cell patch clamp recordings were performed in hypothalamic slices. Both EB and AM251 decreased food intake and weight gain, and increased AMPKα1, AMPKα2 and PI3K p85α gene expression in the mediobasal hypothalamus. 17β-Estradiol rapidly and markedly attenuated the decreases in glutamatergic miniature excitatory postsynaptic current (mEPSC) frequency caused by the cannabinoid receptor agonist WIN 55,212-2 in POMC neurons. This rapid estrogenic diminution of cannabinoid-induced decreases in mEPSC frequency was blocked by the estrogen receptor (ER) antagonist ICI 182,780 and the PI3K inhibitor PI 828, the latter of which also prevented the AM251-induced increase in mEPSC frequency. In addition, the AMPK activator metformin reversed the EB-induced decreases in food intake and weight gain and restored the ability of WIN 55,212-2 to reduce mEPSC frequency. These data reveal that estrogens physiologically antagonize cannabinoid-induced changes in appetite and POMC neuronal activity by activating PI3K and inhibiting AMPK. As such, they provide insight into the neuroanatomical substrates and signal transduction mechanisms upon which these counter-regulatory factors converge in the control of energy homeostasis. Full article
(This article belongs to the Special Issue Medical Marijuana)
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291 KiB  
Article
A Novel Behavioral Fish Model of Nociception for Testing Analgesics
by Ana D. Correia, Sérgio R. Cunha, Martin Scholze and E. Don Stevens
Pharmaceuticals 2011, 4(4), 665-680; https://doi.org/10.3390/ph4040665 - 18 Apr 2011
Cited by 49 | Viewed by 9871
Abstract
Pain is a major symptom in many medical conditions, and often interferes significantly with a person’s quality of life. Although a priority topic in medical research for many years, there are still few analgesic drugs approved for clinical use. One reason is the [...] Read more.
Pain is a major symptom in many medical conditions, and often interferes significantly with a person’s quality of life. Although a priority topic in medical research for many years, there are still few analgesic drugs approved for clinical use. One reason is the lack of appropriate animal models that faithfully represent relevant hallmarks associated with human pain. Here we propose zebrafish (Danio rerio) as a novel short-term behavioral model of nociception, and analyse its sensitivity and robustness. Firstly, we injected two different doses of acetic acid as the noxious stimulus. We studied individual locomotor responses of fish to a threshold level of nociception using two recording systems: a video tracking system and an electric biosensor (the MOBS system). We showed that an injection dose of 10% acetic acid resulted in a change in behavior that could be used to study nociception. Secondly, we validated our behavioral model by investigating the effect of the analgesic morphine. In time-course studies, first we looked at the dose-response relationship of morphine and then tested whether the effect of morphine could be modulated by naloxone, an opioid antagonist. Our results suggest that a change in behavioral responses of zebrafish to acetic acid is a reasonable model to test analgesics. The response scales with stimulus intensity, is attenuated by morphine, and the analgesic effect of morphine is blocked with naloxone. The change in behavior of zebrafish associated with the noxious stimulus can be monitored with an electric biosensor that measures changes in water impedance. Full article
(This article belongs to the Special Issue Opioids)
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Review

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454 KiB  
Review
Molecular Approaches To Target GPCRs in Cancer Therapy
by Giulio Innamorati, Maria Teresa Valenti, Francesco Giovinazzo, Luca Dalle Carbonare, Marco Parenti and Claudio Bassi
Pharmaceuticals 2011, 4(4), 567-589; https://doi.org/10.3390/ph4040567 - 25 Mar 2011
Cited by 15 | Viewed by 9934
Abstract
Hundreds of G protein coupled receptor (GPCR) isotypes integrate and coordinate the function of individual cells mediating signaling between different organs in our bodies. As an aberration of the normal relationships that organize cells’ coexistence, cancer has to deceive cell-cell communication in order [...] Read more.
Hundreds of G protein coupled receptor (GPCR) isotypes integrate and coordinate the function of individual cells mediating signaling between different organs in our bodies. As an aberration of the normal relationships that organize cells’ coexistence, cancer has to deceive cell-cell communication in order to grow and spread. GPCRs play a critical role in this process. Despite the fact that GPCRs represent one of the most common drug targets, current medical practice includes only a few anticancer compounds directly acting on their signaling. Many approaches can be envisaged to target GPCRs involved in oncology. Beyond interfering with GPCRs signaling by using agonists or antagonists to prevent cell proliferation, favor apoptosis, induce maturation, prevent migration, etc., the high specificity of the interaction between the receptors and their ligands can be exploited to deliver toxins, antineoplastic drugs or isotopes to transformed cells. In this review we describe the strategies that are in use, or appear promising, to act directly on GPCRs in the fight against neoplastic transformation and tumor progression. Full article
(This article belongs to the Special Issue GPCR Based Drug Discovery)
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224 KiB  
Review
Role of 5-HT3 Receptors in the Antidepressant Response
by Cécile Bétry, Adeline Etiévant, Chris Oosterhof, Bjarke Ebert, Connie Sanchez and Nasser Haddjeri
Pharmaceuticals 2011, 4(4), 603-629; https://doi.org/10.3390/ph4040603 - 07 Apr 2011
Cited by 56 | Viewed by 13672
Abstract
Serotonin (5-HT)3 receptors are the only ligand-gated ion channel of the 5-HT receptors family. They are present both in the peripheral and central nervous system and are localized in several areas involved in mood regulation (e.g., hippocampus or prefrontal cortex). Moreover, they [...] Read more.
Serotonin (5-HT)3 receptors are the only ligand-gated ion channel of the 5-HT receptors family. They are present both in the peripheral and central nervous system and are localized in several areas involved in mood regulation (e.g., hippocampus or prefrontal cortex). Moreover, they are involved in regulation of neurotransmitter systems implicated in the pathophysiology of major depression (e.g., dopamine or GABA). Clinical and preclinical studies have suggested that 5-HT3 receptors may be a relevant target in the treatment of affective disorders. 5-HT3 receptor agonists seem to counteract the effects of antidepressants in non-clinical models, whereas 5-HT3 receptor antagonists, such as ondansetron, present antidepressant-like activities. In addition, several antidepressants, such as mirtazapine, also target 5-HT3 receptors. In this review, we will report major advances in the research of 5-HT3 receptor’s roles in neuropsychiatric disorders, with special emphasis on mood and anxiety disorders. Full article
(This article belongs to the Special Issue Antidepressants)
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948 KiB  
Review
Functional and Structural Overview of G-Protein-Coupled Receptors Comprehensively Obtained from Genome Sequences
by Makiko Suwa, Minoru Sugihara and Yukiteru Ono
Pharmaceuticals 2011, 4(4), 652-664; https://doi.org/10.3390/ph4040652 - 13 Apr 2011
Cited by 18 | Viewed by 10259
Abstract
An understanding of the functional mechanisms of G-protein-coupled receptors (GPCRs) is very important for GPCR-related drug design. We have developed an integrated GPCR database (SEVENS http://sevens.cbrc.jp/) that includes 64,090 reliable GPCR genes comprehensively identified from 56 eukaryote genome sequences, and overviewed the sequences [...] Read more.
An understanding of the functional mechanisms of G-protein-coupled receptors (GPCRs) is very important for GPCR-related drug design. We have developed an integrated GPCR database (SEVENS http://sevens.cbrc.jp/) that includes 64,090 reliable GPCR genes comprehensively identified from 56 eukaryote genome sequences, and overviewed the sequences and structure spaces of the GPCRs. In vertebrates, the number of receptors for biological amines, peptides, etc. is conserved in most species, whereas the number of chemosensory receptors for odorant, pheromone, etc. significantly differs among species. The latter receptors tend to be single exon type or a few exon type and show a high ratio in the numbers of GPCRs, whereas some families, such as Class B and Class C receptors, have long lengths due to the presence of many exons. Statistical analyses of amino acid residues reveal that most of the conserved residues in Class A GPCRs are found in the cytoplasmic half regions of transmembrane (TM) helices, while residues characteristic to each subfamily found on the extracellular half regions. The 69 of Protein Data Bank (PDB) entries of complete or fragmentary structures could be mapped on the TM/loop regions of Class A GPCRs covering 14 subfamilies. Full article
(This article belongs to the Special Issue GPCR Based Drug Discovery)
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