Spasmolytic Effect of Grewia asiatica Fruit Extract on Isolated Smooth Muscles is Mediated via Multiple Pathways

Background. Grewia asiatica Linn, or phalsa, is a commonly consumed fruit in Pakistan. The fruit is employed in the traditional medicine practice of Pakistan as a smooth muscle relaxant in different gastrointestinal (GI) and cardiovascular diseases. In this investigation, we show the antispasmodic and vasorelaxant actions of Grewia asiatica fruit extract. Methods. A 70% methanolic crude extract of the plant material was prepared (Ga.Cr). Different isolated GI tissue preparations and endothelium-intact aortas from rats were utilized to observe the pharmacological actions of the extract. Results. Ga.Cr, in increasing concentrations, inhibited the spontaneously contracting rabbit jejunum. In an effort to determine the mechanism of this relaxant action, contractions were induced in jejunum and ileum tissues with K+ (80 mM). Ga.Cr was able to only partially inhibit these induced contractions indicating that the mechanism might not be completely through a blockade of Ca2+ channels (CCB). When tested on low K+-(25 mM) sustained contractions, Ga.Cr cumulatively suppressed these contractions (0.1–10 mg/ml), indicating an opening of K+ channels (KCO) as the mechanism. Cromakalim, a standard KCO, was also more specific in blocking low K+-induced contractions. For the effect in aorta tissues, Ga.Cr suppressed the agonist-induced contractions from 0.3 mg/ml to 10 mg/ml. Upon challenge with L-NAME, a nitric oxide (NO) blocker, the extract response curve shifted right, indicating vasodilation was mediated via endothelial NO. Conclusion. This study shows that GI antispasmodic and vasodilator activities of Ga.Cr may be mediated via a KCO mechanism in the GI tract and through the release of NO from vascular endothelium.

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Bitter stimuli induce Ca2+ signaling and CCK release in enteroendocrine STC-1 cells: role of L-type voltage-sensitive Ca2+ channels

AJP Cell Physiology ◽

10.1152/ajpcell.00003.2006 ◽

2006 ◽

Vol 291 (4) ◽

pp. C726-C739 ◽

Cited By ~ 141

Author(s):

Monica C. Chen ◽

S. Vincent Wu ◽

Joseph R. Reeve ◽

Enrique Rozengurt

Keyword(s):

Endocrine Cells ◽

Bitter Taste ◽

Dependent Manner ◽

Gi Tract ◽

Intracellular Ca ◽

Α Subunits ◽

Ca2 Channels ◽

Cck Release

We previously demonstrated the expression of bitter taste receptors of the type 2 family (T2R) and the α-subunits of the G protein gustducin (Gαgust) in the rodent gastrointestinal (GI) tract and in GI endocrine cells. In this study, we characterized mechanisms of Ca2+ fluxes induced by two distinct T2R ligands: denatonium benzoate (DB) and phenylthiocarbamide (PTC), in mouse enteroendocrine cell line STC-1. Both DB and PTC induced a marked increase in intracellular [Ca2+] ([Ca2+]i) in a dose- and time-dependent manner. Chelating extracellular Ca2+ with EGTA blocked the increase in [Ca2+]i induced by either DB or PTC but, in contrast, did not prevent the effect induced by bombesin. Thapsigargin blocked the transient increase in [Ca2+]i induced by bombesin, but did not attenuate the [Ca2+]i increase elicited by DB or PTC. These results indicate that Ca2+ influx mediates the increase in [Ca2+]i induced by DB and PTC in STC-1 cells. Preincubation with the L-type voltage-sensitive Ca2+ channel (L-type VSCC) blockers nitrendipine or diltiazem for 30 min inhibited the increase in [Ca2+]i elicited by DB or PTC. Furthermore, exposure to the L-type VSCCs opener BAY K 8644 potentiated the increase in [Ca2+]i induced by DB and PTC. Stimulation with DB also induced a marked increase in the release of cholecystokinin from STC-1 cells, an effect also abrogated by prior exposure to EGTA or L-type VSCC blockers. Collectively, our results demonstrate that bitter tastants increase [Ca2+]i and cholecystokinin release through Ca2+ influx mediated by the opening of L-type VSCCs in enteroendocrine STC-1 cells.

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Solitary Peutz-Jeghers Type Polyp of Jejunum with Gastric Fundic and Antral Gland Lining Mucosa: A Case Report and Review of Literature

International Journal of Surgical Pathology ◽

10.1177/10668969211067760 ◽

2021 ◽

pp. 106689692110677

Author(s):

Bella Lingjia Liu ◽

Huifang Zhou ◽

Martina Risech ◽

Alex Ky ◽

Jane Houldsworth ◽

...

Keyword(s):

Family History ◽

Small Bowel ◽

Smooth Muscles ◽

Fundic Gland ◽

Muscularis Mucosa ◽

Hamartomatous Polyp ◽

Gi Tract ◽

First Case ◽

Mucocutaneous Pigmentation ◽

Peutz Jeghers Syndrome

Solitary Peutz-Jeghers type polyps are characterized by a hamartomatous polyp of the gastrointestinal (GI) tract in a patient without mucocutaneous pigmentation, family history of Peutz-Jeghers syndrome, or STK11/LKB1 mutations. Histologically identical to the polyps in Peutz-Jeghers syndrome, these sporadic polyps can arise anywhere along the GI tract, with typical arborizing smooth muscles extending from the muscularis mucosa. While the lining mucosa is generally the same as the organ in which it arises, gastric pyloric and osseous metaplasia have been reported in intestinal polyps in Peutz-Jeghers syndrome. Herein, the authors report the first case of a small intestinal solitary Peutz-Jeghers type polyp with gastric antral and fundic gland lining mucosa. A 43-year-old male was admitted for small bowel obstruction. Diagnostic laparoscopy revealed jejuno-jejunal intussusception with an associated polyp measuring 7.2 cm. Histological examination showed a hamartomatous polyp with arborizing smooth muscle bundles extending from the muscularis mucosae. The polyp was lined by non-dysplastic gastric antral and fundic gland mucosa, and was sharply demarcated from the adjacent non-polypoid intestinal mucosa. Colonoscopy, esophagogastroduodenoscopy and small bowel enteroscopy revealed no additional polyps or masses. Thorough investigation of the patient's family history was negative for Peutz-Jeghers syndrome or mucocutaneous pigmentation. Molecular analysis of the lesion was negative for STK11/LKB1 mutations. A diagnosis of solitary Peutz-Jeghers type polyp of the small bowel with gastric antral and fundic gland mucosal lining was rendered.

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Molecular diversity of KVα- and β-subunit expression in canine gastrointestinal smooth muscles

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1999.277.1.g127 ◽

1999 ◽

Vol 277 (1) ◽

pp. G127-G136 ◽

Cited By ~ 10

Author(s):

Anne Epperson ◽

Helena P. Bonner ◽

Sean M. Ward ◽

William J. Hatton ◽

Karri K. Bradley ◽

...

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Smooth Muscles ◽

Muscle Cells ◽

Pcr Analysis ◽

Transcriptional Level ◽

Gi Tract ◽

Excitable Cells ◽

Subunit Expression ◽

Molecular Components

Voltage-activated K+(KV) channels play an important role in regulating the membrane potential in excitable cells. In gastrointestinal (GI) smooth muscles, these channels are particularly important in modulating spontaneous electrical activities. The purpose of this study was to identify the molecular components that may be responsible for the KV currents found in the canine GI tract. In this report, we have examined the qualitative expression of eighteen different KV channel genes in canine GI smooth muscle cells at the transcriptional level using RT-PCR analysis. Our results demonstrate the expression of KV1.4, KV1.5, KV1.6, KV2.2, and KV4.3 transcripts in all regions of the GI tract examined. Transcripts encoding KV1.2, KVβ1.1, and KVβ1.2 subunits were differentially expressed. KV1.1, KV1.3, KV2.1, KV3.1, KV3.2, KV3.4, KV4.1, KV4.2, and KVβ2.1 transcripts were not detected in any GI smooth muscle cells. We have also determined the protein expression for a subset of these KV channel subunits using specific antibodies by immunoblotting and immunohistochemistry. Immunoblotting and immunohistochemistry demonstrated that KV1.2, KV1.4, KV1.5, and KV2.2 are expressed at the protein level in GI tissues and smooth muscle cells. KV2.1 was not detected in any regions of the GI tract examined. These results suggest that the wide array of electrical activity found in different regions of the canine GI tract may be due in part to the differential expression of KV channel subunits.

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Ca2+ channel blockers distinguish between G protein-coupled pharmacomechanical Ca2+ release and Ca2+ sensitization

AJP Cell Physiology ◽

10.1152/ajpcell.1991.260.2.c364 ◽

1991 ◽

Vol 260 (2) ◽

pp. C364-C370 ◽

Cited By ~ 53

Author(s):

S. Kobayashi ◽

M. C. Gong ◽

A. V. Somlyo ◽

A. P. Somlyo

Keyword(s):

Phospholipase C ◽

G Protein ◽

Smooth Muscles ◽

Channel Blockers ◽

Alpha Toxin ◽

Adrenergic Agonist ◽

Pharmacomechanical Coupling ◽

Gamma S ◽

G Protein Coupled ◽

Ca2 Channels

The effects of Ca2+ channel blockers on two modes of G protein-mediated pharmacomechanical coupling, Ca2+ release and modulation of Ca2+ sensitivity of the contractile apparatus, were investigated. Smooth muscles were permeabilized with Staphylococcal alpha-toxin or with beta-escin to avoid effects due to block of sarcolemmal Ca2+ channels, while retaining receptor/G protein coupling. In permeabilized portal vein smooth muscle, verapamil and nifedipine inhibited Ca2+ release induced by an alpha 1-adrenergic agonist (phenylephrine) and by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), but not that induced by inositol 1,4,5-trisphosphate (InsP3). These Ca2+ channel blockers also did not block the phenylephrine- or GTP gamma S-induced force development at constant cytoplasmic Ca2+ ("Ca2+ sensitization"). An alpha 1-blocker (prazosin) inhibited both the Ca2(+)-releasing and Ca2(+)-sensitizing effects of phenylephrine, but not those of GTP gamma S, nor did it block InsP3-induced Ca2+ release. We conclude that Ca2+ channel blockers selectively uncouple the Ca2(+)-releasing, but not the Ca2(+)-sensitizing, component of pharmacomechanical coupling. These findings raise the possibility that pharmacomechanical Ca2+ release may be modulated by dihydropyridine binding proteins at the level of G proteins/phospholipase C and also indicate a divergence of the Ca2(+)-releasing and Ca2(+)-sensitizing effects at some step prior to phospholipase C.

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A novel peptide vasoconstrictor, endothelin, is produced by vascular endothelium and modulates smooth muscle Ca2+ channels

Journal of Hypertension ◽

10.1097/00004872-198812040-00056 ◽

1988 ◽

Vol 6 (4) ◽

pp. S188-191 ◽

Cited By ~ 173

Author(s):

Masashi Yanagisawa ◽

Hiroki Kurihara ◽

Sadao Kimura ◽

Katsutoshi Goto ◽

Tomoh Masaki

Keyword(s):

Smooth Muscle ◽

Vascular Endothelium ◽

Ca2 Channels

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Toxicity and Cellular Uptake of Gold Nanorods in Vascular Endothelium and Smooth Muscles of Isolated Rat Blood Vessel: Importance of Surface Modification

Small ◽

10.1002/smll.201101948 ◽

2012 ◽

Vol 8 (8) ◽

pp. 1270-1278 ◽

Cited By ~ 52

Author(s):

Alaaldin M. Alkilany ◽

Alia Shatanawi ◽

Timothy Kurtz ◽

Ruth B. Caldwell ◽

R. William Caldwell

Keyword(s):

Surface Modification ◽

Blood Vessel ◽

Cellular Uptake ◽

Gold Nanorods ◽

Vascular Endothelium ◽

Smooth Muscles ◽

Rat Blood ◽

Isolated Rat

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The new inhibitory agents of receptor operated Ca2+ channels and intracellular Ca2+ release in the vascular smooth muscles

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)58895-3 ◽

1986 ◽

Vol 40 ◽

pp. 13

Author(s):

Nobuhiro Satake ◽

Hachiro Usui ◽

Kazuyoshi Kurahashi ◽

Motohatsu Fujiwara ◽

Shoji Shibata

Keyword(s):

Smooth Muscles ◽

Vascular Smooth Muscles ◽

Inhibitory Agents ◽

Ca2 Channels

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Impact of a Newly Synthesized Molecule (2-chloro-N-(1-(3,4-dimethoxyphenyl) propan-2-yl)-2-phenylacetamide) on the Bioelectrogenesis and the Contractile Activity of Isolated Smooth Muscles

Folia Medica ◽

10.3897/folmed.62.e47844 ◽

2020 ◽

Vol 62 (3) ◽

pp. 532-538

Author(s):

Vera N. Gledacheva ◽

Iliyana D. Stefanova ◽

Valeri I. Slavchev ◽

Rayna G. Ardasheva ◽

Atanas D. Kristev ◽

...

Keyword(s):

Contractile Activity ◽

Muscle Relaxation ◽

Smooth Muscles ◽

Mechanical Activity ◽

Aziridine Ring ◽

Male Wistar Rats ◽

Dependent Signal ◽

Sucrose Gap ◽

Relaxing Effect ◽

Ca2 Channels

Introduction: Examination of the potential possibilities of 2-chloro-N-(1-(3,4-dimethoxyphenyl)propan-2-yl)-2-phenylacetamide (IQP) to affect bioelectrogenesis and the contractile activity of isolated smooth muscles (SM) from stomach. Aim: Having in mind the structural similarities between the molecules of papaverine and IQP, the aim of the present study was to examine such features of the newly synthesized molecule that may potentially affect the muscle tonus, spontaneous bioelectrical and contractile activities of smooth muscles isolated from the stomach, basing on specific mechanisms of papaverine. Materials and methods: The synthesis of IQP is based on the initially formed aziridine ring by principles of Gilbert’s reaction. Impact of IQP on the bioelectrogenesis and the contractile activity of isolated smooth muscles from male Wistar rats was measured by the single sucrose-gap method and isometrically recorded. Results: IQP (1×10-5 – 2.5×10-4 mol/l) causes muscle relaxation, producing changes in two processes that have influence on the mechanical activity of smooth muscles:1.    Blocked Ca2+ influx through the potential-dependent membrane Ca2+ channels, followed in turn by lowering the Ca2+ intracellular levels. This effect is proved by the changes in the frequency and amplitude of spike-potentials in sucrose-bridge experiments when IQP is applied.2.    Activation of a cAMP-dependent signal cascade. The relaxing effect of IQP was significantly reduced in the presence of KT5720(5×10-6 mol/l), an inhibitor of protein kinase A. Conclusion: We assume that there might be interconnections between these two IQP-dependent processes, because PKA-dependent phosphorylation of the L-type Ca2+ channels in smooth muscles provokes a reaction of inactivation.

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The role of Ni2+-sensitive T-type Ca2+ channels in the regulation of spontaneous excitation in detrusor smooth muscles of the guinea-pig bladder

BJU International ◽

10.1111/j.1464-410x.2006.05894.x ◽

2006 ◽

Vol 97 (1) ◽

pp. 182-189 ◽

Cited By ~ 18

Author(s):

YOSHIMASA YANAI ◽

HIKARU HASHITANI ◽

YASUE KUBOTA ◽

SHOICHI SASAKI ◽

KENJIRO KOHRI ◽

...

Keyword(s):

Guinea Pig ◽

Smooth Muscles ◽

Ca2 Channels

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Antidiarrheal and antispasmodic activities of Polygonum bistorta rhizomes are mediated predominantly through K+ channels activation

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v10i3.23714 ◽

2015 ◽

Vol 10 (3) ◽

pp. 627 ◽

Cited By ~ 3

Author(s):

Muhammad Zeeshan Ali ◽

Khalid Hussain Janbaz ◽

Malik Hassan Mehmood ◽

Anwar Hassan Gilani

Keyword(s):

Tetraethylammonium Chloride ◽

Relaxant Effect ◽

Complete Relaxation ◽

High K ◽

Rabbit Jejunum ◽

Low K ◽

Dose Dependent ◽

Antagonist Effect

Polygonum bistorta is a popular medicinal herb used to treat diarrhea. This study provides pharmacological basis to its folk use in diarrhea using in vivo and in vitro assays. Administration of P. bistorta rhizomes extract to mice offered protection against castor oil-induced diarrhea at 300-1,000 mg/kg and was found safe up to the dose of 5 g/kg. In isolated rabbit jejunum, the extract caused a dose-dependent relaxation of spontaneous and low K+ (25 mM)-induced contractions with weak effect against high K+ (80 mM). In tissues pretreated with glibenclamide or tetraethylammonium chloride (TEA), the relaxant effect of the extract was markedly inhibited by TEA only. While verapamil showed complete relaxation of spontaneous, low K+, low K+ with TEA and high K+-induced contractions. In guinea-pig ileum, mild atropine-sensitive effect was observed. This study indicates that P. bistorta possesses anti-diarrheal and antispasmodic activities mediated predominantly through K+-channels activation along with weak Ca++ antagonist effect.

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