AG-041R, a Gastrin/CCK-B Antagonist, Stimulates Chondrocyte Proliferation and Metabolism in Vitro

Ochi, Mitsuo; Kawasaki, Kenzo; Kataoka, Hiroko; Uchio, Yuji; Nishi, Hideaki

doi:10.1006/bbrc.2001.4911

Cited by 179 publications

(69 citation statements)

References 14 publications

(11 reference statements)

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“…Single strand cDNA was synthesized from 5 μg of total RNA using the Superscript Preamplification System (Gibco BRL) with a random hexamer. PCR reaction was performed with EX Taq DNA polymerase (Takara Biochemicals, Kyoto) using primer sets as reported previously (21). The primer sequences for rabbit collagen type I, collagen type II, and glyceraldehyde-3-phosphate dehydrogenase (G3PDH) were as follows (from 5' to 3'): GTG GTC CCC CTG GTG CTG TG (sense, position 197 -216) and TCC GTT GTG TCC CTT TAT GC (antisense, position 561-542, GenBank accession number D49399) for collagen type-I α2 subunit (COL1A2); CCA CGC TCA AGT CCC TCA A (sense, position 71 -89) and ACG GTC TTG CCC CAC TTA C (antisense, position 647 -629, GenBank accession number D83228) for collagen type-II α1 subunit (COL2A1); and GCC AAA AGG GTC ATC ATC AT (sense, position 22 -39) and GCC TGC TTC ACC ACC TTC TT (antisense, position 470 -451, GenBank accession number AB231852) for G3PDH.…”

Section: Reverse-transcriptase Polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

Swelling-Activated Cl− Current in Isolated Rabbit Articular Chondrocytes: Inhibition by Arachidonic Acid

et al. 2009

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Abstract. Articular chondrocytes play an important role in maintaining the structure and function of the cartilage in synovial joints, which is closely influenced by mechanical or osmotic stress. In the present study, isolated rabbit articular chondrocytes were examined during hyposmotic stress using the whole-cell patch-clamp method. When exposed to hyposmotic external solutions (approximately 5% or 32% decrease in osmolarity), isolated rabbit articular chondrocytes exhibited hyposmotic cell swelling, accompanied by the activation of the swellingactivated Cl − current (I Cl,swell ). I Cl,swell was practically time-independent at potentials negative to +50 mV but exhibited rapid inactivation at more positive potentials. I Cl,swell was potently inhibited by the Cl − channel blockers 5-nitro-2-(3-phenylpropylamino)benzoic acid, glibenclamide, and tamoxifen, but was little affected by pimozide. I Cl,swell was also found to be acutely inhibited by arachidonic acid in a concentration-dependent manner with an IC 50 of 0.81 μM. The maximal effect (approximately 100% block) was obtained with 10 μM arachidonic acid. The arachidonic acid metabolites prostaglandin E 2 , leukotriene B 4 , and leukotriene D 4 had no appreciable effect on I Cl,swell , suggesting that the inhibitory effect of arachidonic acid did not require its metabolism. The present study thus reveals the presence of I Cl,swell in rabbit articular chondrocytes that exhibits high sensitivity to direct inhibition by arachidonic acid.

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Section: Reverse-transcriptase Polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

Swelling-Activated Cl− Current in Isolated Rabbit Articular Chondrocytes: Inhibition by Arachidonic Acid

et al. 2009

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“…For engineered cartilage, many researchers have been studying the extracellular matrix either biochemically or biomechanically. [12][13][14] However, both biochemical and biomechanical studies on engineered cartilage have been limited. In the present study, engineered cartilage was studied both biochemically and biomechanically.…”

Section: Introductionmentioning

confidence: 99%

Usefulness of Photoacoustic Measurements for Evaluation of Biomechanical Properties of Tissue-Engineered Cartilage

Ishihara

Sato²,

Sato³

et al. 2005

Tissue Engineering

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There is a demand in the field of regenerative medicine for measurement technology that enables functions of engineered tissue to be determined. For meeting this demand, we previously proposed a noninvasive method for determination of the viscoelasticity of a tissue phantom based on photoacoustic measurements. The purpose of this study was to verify the usefulness of the photoacoustic measurement method for evaluation of the viscoelastic properties of actual engineered tissue and to determine the correlation between biochemical characteristics and photoacoustic signals. The relaxation times measured by the photoacoustic method agreed well with the intrinsic viscoelastic parameters with a correlation coefficient of 0.98 when tissue-engineered cartilage tissues cultured for various periods (up to 12 weeks) were used as samples. By comparison of the results of biochemical analyses and biomechanical studies, we proved that the photoacoustic signal is a good indicator for evaluating extracellular matrix formation in order to determine the characteristics of tissue-engineered cartilage. To our knowledge, this is the first report on noninvasive and time-dependent viscoelastic evaluation of engineered tissue for determining functions of engineered tissues.

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“…259 Additionally, AG-041R induced systemic cartilage hyperplasia by stimulation of chondrocyte proliferation and metabolism, an intrinsic property of this compound no related with its CCK 2 receptor antagonism. 260,261 AG-041R also stimulated the repair of osteochondrial defects in a rabbit model. 262 These findings suggest that this compound could be a therapeutic agent for cartilage disorders.…”

Section: K Indol-2-one-based Cck Antagonistsmentioning

confidence: 95%

Cholecystokinin antagonists: Pharmacological and therapeutic potential

Herranz

2003

Medicinal Research Reviews

167

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Cholecystokinin (CCK) is a regulatory peptide hormone, predominantly found in the gastrointestinal tract, and a neurotransmitter present throughout the nervous system. In the gastrointestinal system CCK regulates motility, pancreatic enzyme secretion, gastric emptying, and gastric acid secretion. In the nervous system CCK is involved in anxiogenesis, satiety, nociception, and memory and learning processes. Moreover, CCK interacts with other neurotransmitters in some areas of the CNS. The biological effects of CCK are mediated by two specific G protein coupled receptor subtypes, termed CCK(1) and CCK(2). Over the past fifteen years the search of CCK receptor ligands has evolved from the initial CCK structure derived peptides towards peptidomimetic or non-peptide agonists and antagonists with improved pharmacokinetic profile. This research has provided a broad assortment of potent and selective CCK(1) and CCK(2) antagonists of diverse chemical structure. These antagonists have been discovered through optimization programs of lead compounds which were designed based on the structures of the C-terminal tetrapeptide, CCK-4, or the non-peptide natural compound, asperlicin, or derived from random screening programs. This review covers the main pharmacological and therapeutic aspects of these CCK(1) and CCK(2) antagonist. CCK(1) antagonists might have therapeutic potential for the treatment of pancreatic disorders and as prokinetics for the treatment of gastroesophageal reflux disease, bowel disorders, and gastroparesis. On the other hand, CCK(2) antagonists might have application for the treatment of gastric acid secretion and anxiety disorders.

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AG-041R, a Gastrin/CCK-B Antagonist, Stimulates Chondrocyte Proliferation and Metabolism in Vitro

Cited by 179 publications

References 14 publications

Swelling-Activated Cl− Current in Isolated Rabbit Articular Chondrocytes: Inhibition by Arachidonic Acid

Swelling-Activated Cl− Current in Isolated Rabbit Articular Chondrocytes: Inhibition by Arachidonic Acid

Usefulness of Photoacoustic Measurements for Evaluation of Biomechanical Properties of Tissue-Engineered Cartilage

Cholecystokinin antagonists: Pharmacological and therapeutic potential

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