Charles D Anderson, Derek M Kendig, Mohammad Al-Qudah, Sunila Mahavadi, Karnam S Murthy, John R Grider
{"title":"Role of various kinases in muscarinic M3 receptor-mediated contraction of longitudinal muscle of rat colon.","authors":"Charles D Anderson, Derek M Kendig, Mohammad Al-Qudah, Sunila Mahavadi, Karnam S Murthy, John R Grider","doi":"10.1540/jsmr.50.103","DOIUrl":"https://doi.org/10.1540/jsmr.50.103","url":null,"abstract":"<p><p>The longitudinal muscle layer in gut is the functional opponent to the circular muscle layer during peristalsis. Differences in innervation of the layers allow for the contraction of one layer concurrently with the relaxation of the other, enabling the passage of gut contents in a controlled fashion. Differences in development have given the cells of the two layers differences in receptor populations, membrane lipid handling, and calcium handling profiles/behaviors. The contractile activity of the longitudinal muscle is largely mediated by cholinergic neural input from myenteric plexus. Activation of muscarinic receptors leads to rapid activation of several kinases including MLC kinase, ERK1/2, CaMKII and Rho kinase. Phosphorylation of myosin light chain (MLC20) by MLC kinase (MLCK) is a prerequisite for contraction in both circular and longitudinal muscle cells. In rat colonic longitudinal muscle strips, we measured muscarinic receptor-mediated contraction following incubation with kinase inhibitors. Basal tension was differentially regulated by Rho kinase, ERK1/2, CaMKII and CaMKK. Selective inhibitors of Rho kinase, ERK1/2, CaMKK/AMPK, and CaMKII each reduced carbachol-induced contraction in the innervated muscle strips. These inhibitors had no direct effect on MLCK activity. Thus unlike previously reported for isolated muscle cells where CaMKII and ERK1/2 are not involved in contraction, we conclude that the regulation of carbachol-induced contraction in innervated longitudinal muscle strips involves the interplay of Rho kinase, ERK1/2, CaMKK/AMPK, and CAMKII. </p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"50 ","pages":"103-19"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.50.103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33232993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Onesmo B Balemba, Timo D Stark, Sofie Lösch, Savannah Patterson, John S McMillan, Gary M Mawe, Thomas Hofmann
{"title":"(2R,3S,2'' R,3''R)-manniflavanone, a new gastrointestinal smooth muscle L-type calcium channel inhibitor, which underlies the spasmolytic properties of Garcinia buchananii stem bark extract.","authors":"Onesmo B Balemba, Timo D Stark, Sofie Lösch, Savannah Patterson, John S McMillan, Gary M Mawe, Thomas Hofmann","doi":"10.1540/jsmr.50.48","DOIUrl":"https://doi.org/10.1540/jsmr.50.48","url":null,"abstract":"<p><p>Garcinia buchananii Baker stem bark extract (GBB) is a traditional medication of diarrhea and dysentery in sub-Saharan Africa. It is believed that GBB causes gastrointestinal smooth muscle relaxation. The aim of this study was to determine whether GBB has spasmolytic actions and identify compounds underlying these actions. Calcium (Ca(2+)) imaging was used to analyze the effect of GBB on Ca(2+) flashes and Ca(2+) waves in guinea pig gallbladder and distal colon smooth muscle. Intracellular microelectrode recording was used to determine the effect of GBB, six fractions of GBB, M1-5 and M7, and (2R,3S,2'' R,3''R)-manniflavanone, a compound isolated from M3 on action potentials in gallbladder smooth muscle. The technique was also used to analyze the effect of GBB, M3, and (2R,3S,2'' R,3''R)-manniflavanone on action potentials in the circular muscle of mouse and guinea pig distal colons, and the effect of GBB and (2R,3S,2''R,3'' R)-manniflavanone on slow waves in porcine ileum. GBB inhibited Ca(2+) flashes and Ca(2+) waves. GBB, M3 and (2R,3 S,2''R,3''R)-manniflavanone inhibited action potentials. L-type Ca(2+) channel activator Bay K 8644 increased the discharge of action potentials in mouse colon but did not trigger or increase action potentials in the presence of GBB and (2R,3S,2''R,3'' R)-manniflavanone. GBB and (2R,3S,2'' R,3''R)-manniflavanone inhibited action potentials in the presence of Bay K 8644. GBB and (2R,3 S,2''R,3''R)-manniflavanone reduced the amplitude but did not alter the frequency of slow waves in the porcine ileum. In conclusion, GBB and (2R,3S,2'' R,3''R)-manniflavanone relax smooth muscle by inhibiting L-type Ca(2+) channels, thus have potential for use as therapies of gastrointestinal smooth muscle spasms, and arrhythmias. </p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"50 ","pages":"48-65"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.50.48","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33394771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Swati Kundu, Hiba Shabir, Seemi Farhat Basir, Luqman Ahmad Khan
{"title":"Inhibition of As(III) and Hg(II) caused aortic hypercontraction by eugenol, linalool and carvone.","authors":"Swati Kundu, Hiba Shabir, Seemi Farhat Basir, Luqman Ahmad Khan","doi":"10.1540/jsmr.50.93","DOIUrl":"https://doi.org/10.1540/jsmr.50.93","url":null,"abstract":"<p><p>Acute and chronic exposure to arsenic and mercury is known to produce vasoconstriction. There is, however, no clarity concerning the pathways leading to this increased contraction. In this study we elicit and compare maximum contractility of rat aortas under resting conditions in the presence of arsenic and mercury, and delineate pathways mediating this effect. Phenylephrine (PE) induced hypercontraction of 37% and 32% were obtained when isolated aortic segments were exposed to 25 ?M As(III) and 6 nM Hg(II), respectively. Isometric contraction measurements in presence of apocynin, verapamil and sodium nitroprusside indicates that the major causes of increased contraction are reactive oxygen species (ROS) and depletion of nitric oxide (NO). Calcium influx plays a minor role in arsenic and mercury caused hypercontraction. In unexposed aorta, eugenol causes relaxation by inhibiting ROS and elevating NO, linalool by blocking voltage dependent calcium channel (VDCC) and elevating NO, and carvone by blocking calcium influx through VDDC. Since the arsenic and mercury hypercontraction is mediated by increased ROS and depleted NO, we hypothesize that molecules which neutralize ROS or elevate NO will be better ameliorators. In line with this argument, we found eugenol to be the best ameliorator of arsenic and mercury hypercontraction followed by linalool and carvone. </p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"50 ","pages":"93-102"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.50.93","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33232991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kosuke Takeya, Xuemei Wang, Cindy Sutherland, Iris Kathol, Kathy Loutzenhiser, Rodger D Loutzenhiser, Michael P Walsh
{"title":"Involvement of myosin regulatory light chain diphosphorylation in sustained vasoconstriction under pathophysiological conditions.","authors":"Kosuke Takeya, Xuemei Wang, Cindy Sutherland, Iris Kathol, Kathy Loutzenhiser, Rodger D Loutzenhiser, Michael P Walsh","doi":"10.1540/jsmr.50.18","DOIUrl":"https://doi.org/10.1540/jsmr.50.18","url":null,"abstract":"<p><p>Smooth muscle contraction is activated primarily by phosphorylation at Ser19 of the regulatory light chain subunits (LC20) of myosin II, catalysed by Ca(2+)/calmodulin-dependent myosin light chain kinase. Ca(2+)-independent contraction can be induced by inhibition of myosin light chain phosphatase, which correlates with diphosphorylation of LC20 at Ser19 and Thr18, catalysed by integrin-linked kinase (ILK) and zipper-interacting protein kinase (ZIPK). LC20 diphosphorylation at Ser19 and Thr18 has been detected in mammalian vascular smooth muscle tissues in response to specific contractile stimuli (e.g. endothelin-1 stimulation of rat renal afferent arterioles) and in pathophysiological situations associated with hypercontractility (e.g. cerebral vasospasm following subarachnoid hemorrhage). Comparison of the effects of LC 20 monophosphorylation at Ser19 and diphosphorylation at Ser19 and Thr18 on contraction and relaxation of Triton-skinned rat caudal arterial smooth muscle revealed that phosphorylation at Thr18 has no effect on steady-state force induced by Ser19 phosphorylation. On the other hand, the rates of dephosphorylation and relaxation are significantly slower following diphosphorylation at Thr18 and Ser19 compared to monophosphorylation at Ser19. We propose that this diphosphorylation mechanism underlies the prolonged contractile response of particular vascular smooth muscle tissues to specific stimuli, e.g. endothelin-1 stimulation of renal afferent arterioles, and the vasospastic behavior observed in pathological conditions such as cerebral vasospasm following subarachnoid hemorrhage and coronary arterial vasospasm. ILK and ZIPK may, therefore, be useful therapeutic targets for the treatment of such conditions. </p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"50 ","pages":"18-28"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.50.18","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32295733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of colonic distension on gastric adaptive relaxation in rats: barostatic evaluation using an orally introduced gastric balloon.","authors":"Masayuki Uchida, Chizuru Iwamoto","doi":"10.1540/jsmr.50.78","DOIUrl":"https://doi.org/10.1540/jsmr.50.78","url":null,"abstract":"<p><p>While the gastrocolonic reflex has been known, the cologastric relationship has not been clarified especially with regard to gastric adaptive relaxation. Therefore, in this study we have examined the correlation between gastric adaptive relaxation and colonic distension. Male Sprague-Dawley rats were used after fasting for 18 hrs. Colonic distension was performed by injecting 2.2 ml of air into a colonic balloon inserted into the colon for 5 min in conscious state. After urethane anesthesia, gastric adaptive relaxation was investigated by using a slightly modified gastric balloon introduced into the stomach through the mouth. Gastric balloon volumes increased gradually just after an increment in the gastric balloon pressure (1 to 8 mmHg), and reached a plateau within 1 min. This increased volume was defined as gastric adaptive relaxation. In control rats, gastric adaptive relaxation increased with pressure increments in a pressure dependent manner. In the colon-distended rats, gastric adaptive relaxation increased also in a pressure dependent manner, but was significantly inhibited as compared with control at 8 mmHg (P<0.05). These findings show that colonic distension inhibits the gastric adaptive relaxation and suggests the existence of a cologastric relationship in rats. </p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"50 ","pages":"78-84"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cc/a9/jsmr-50-078.PMC5137303.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33394772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bano Saidullah, Kambadur Muralidhar, Mohammad Fahim
{"title":"Onset of diabetes modulates the airway smooth muscle reactivity of guinea pigs: role of epithelial mediators.","authors":"Bano Saidullah, Kambadur Muralidhar, Mohammad Fahim","doi":"10.1540/jsmr.50.29","DOIUrl":"https://doi.org/10.1540/jsmr.50.29","url":null,"abstract":"<p><strong>Background: </strong>Diabetes induces lung dysfunction, leading to alteration in the pulmonary functions. Our aim was to investigate whether the early stage of diabetes alters the epithelium-dependent bronchial responses and whether nitric oxide (NO), KATP channels and cyclooxygenase (COX) pathways contribute in this effect.</p><p><strong>Methods: </strong>Guinea pigs were treated with a single injection of streptozotocin (180 mg/kg, i.p.) for induction of diabetes. Airway conductivity was assessed by inhaled histamine, using a non-invasive body plethysmography. The contractile responses of tracheal rings induced by acetylcholine (ACh) and relaxant responses of precontracted rings, induced by isoproterenol (IP) were compared in the presence and absence of the epithelium. Effects of N(ω)-Nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor), glybenclamide (a KATP channel inhibitor) and indomethacin (a COX inhibitor) were also assessed in diabetic guinea pigs.</p><p><strong>Results: </strong>Early stage diabetes did not alter the airway conductivity. ACh-induced bronchoconstriction in epithelium intact tracheal rings was not affected by the onset of diabetes, however a reduction in the increased ACh responses due to epithelium removal, to L-NAME or to indomethacin was observed. The relaxation response to IP was impaired in trachea from guinea pigs in which diabetes had just developed. Early diabetes significantly reduced the IP response to glybenclamide and to indomethacin.</p><p><strong>Conclusion: </strong>Our results demonstrate that the early stage of diabetes, modulate the bronchial reactivity to both ACh and IP by disrupting the NO, KATP channels and COX pathways, without affecting the airway conductivity in guinea pigs.</p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"50 ","pages":"29-38"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0f/b6/jsmr-50-029.PMC5137320.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32342426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correlations between anxiety and the stress responses of electrogastrography (EGG) induced by the mirror drawing test (MDT).","authors":"Shinji Homma","doi":"10.1540/jsmr.50.1","DOIUrl":"https://doi.org/10.1540/jsmr.50.1","url":null,"abstract":"<p><p>Electrogastrograms (EGGs) were recorded at 16 locations on the thoraco-abdominal surface at rest and then both during and after the acute stress of performing the mirror drawing test (MDT). A significant linear correlation with a negative slope was found between the anxiety scores and the ratio of the power content during MDT to the power content at rest (r) (MDTr(-1)) of the 3 cpm component from the epigastric channel 2 recording. In contrast, significant linear correlations with positive slopes were found between the anxiety scores and MDTr(-1) of the 6 cpm component of the recordings from the infraumbilical channels (channels 13, 15, and 16). The epigastric 3-cpm EGG activity reflects gastric myoelectric activity, while the infraumbilical 3- and 6-cpm activity reflects that of the colon. Therefore, these results seem to further support the previous report of the inhibition of gastric EGG by stress and the stress-mediated facilitation of colonic EGG (Homma S, J Smooth Muscle Res. 2012; 48(2-3): 47-57).</p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"50 ","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.50.1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32295731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pathological function of Ca2+-sensing receptor in pulmonary arterial hypertension.","authors":"Aya Yamamura","doi":"10.1540/jsmr.50.8","DOIUrl":"https://doi.org/10.1540/jsmr.50.8","url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) is defined as an intractable disease characterized by a progressive elevation of pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP), leading to right heart failure and premature death. The five-year survival rate after diagnosis is approximately 57%. Although extensive research has identified some factors associated with the cause of PAH, the etiology and pathogenesis remain unclear. In addition to Ca(2+) channel blockers (nifedipine, diltiazem), three categories of drug have been developed for the treatment of PAH based on the pathological mechanisms: prostacyclin and its analogues (epoprostenol, treprostinil, iloprost), endothelin receptor antagonists (bosentan, ambrisentan), and phosphodiesterase type 5 inhibitors (sildenafil, tadalafil). However, screening of novel types of drug acting on the signal pathway associated with the pathological mechanism underlying PAH is ongoing. We recently found that the extracellular Ca(2+)-sensing receptor (CaSR), which belongs to family C of the G protein-coupled receptor (GPCR) superfamily, is upregulated in pulmonary arterial smooth muscle cells (PASMCs) from patients with idiopathic PAH (IPAH). The upregulated CaSR is necessary for the enhanced Ca(2+) signaling and the augmented cell proliferation in PASMCs from IPAH patients. Most importantly, blockage of CaSR with an antagonist, NPS2143, prevents the development of pulmonary hypertension and right ventricular hypertrophy in animal models of pulmonary hypertension. The use of calcilytics, antagonists of CaSR, may be a novel therapeutic approach for PAH patients.</p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"50 ","pages":"8-17"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.50.8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32295732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Italo R R Martins, Rosimeire F Dos Santos, Ana C de C Correia, Gislaine A de Oliveira, Cibério L Macêdo, Fabio de S Monteiro, Paula F Dos Santos, Fabiana de A Cavalcante, Josean F Tavares, Bagnólia A da Silva
{"title":"Relaxant effect of Ent-7α-hydroxytrachyloban-18-oic acid, a trachylobane diterpene from Xylopia langsdorfiana A. St-Hil. & Tul., on tracheal smooth muscle.","authors":"Italo R R Martins, Rosimeire F Dos Santos, Ana C de C Correia, Gislaine A de Oliveira, Cibério L Macêdo, Fabio de S Monteiro, Paula F Dos Santos, Fabiana de A Cavalcante, Josean F Tavares, Bagnólia A da Silva","doi":"10.1540/jsmr.49.15","DOIUrl":"https://doi.org/10.1540/jsmr.49.15","url":null,"abstract":"<p><p>Ent-7α-hydroxytrachyloban-18-oic acid, a trachylobane diterpene from Xylopia langsdorfiana, has previously been shown to relax the guinea-pig trachea in a concentration-dependent manner. In this study we aimed to elucidate the mechanisms underlying this action and so contribute to the discovery of natural products with therapeutic potential. A possible interaction between diterpene and the Ca(2+)-calmodulin complex was eliminated as chlorpromazine (10(-6) M), a calmodulin inhibitor, did not significantly alter the diterpene-induced relaxation (pD2 = 4.38 ± 0.07 and 4.25 ± 0.07; mean ± S.E.M., n=5). Trachylobane-318 showed a higher relaxant potency when the trachea was contracted by 18 mM KCl than it did with 60 mM KCl (pD2 = 4.90 ± 0.25 and 3.88 ± 0.01, n=5), suggesting the possible activation of K(+) channels. This was confirmed, as in the presence of 10 mM TEA(+) (a non-selective K(+) channel blocker), diterpene relaxation potency was significantly reduced (pD2 = 4.38 ± 0.07 to 4.01 ± 0.06, n=5). Furthermore, K(+) channel subtypes KATP, KV, SKCa and BKCa seem to be modulated positively by trachylobane-318 (pD2 = 3.91 ± 0.003, 4.00 ± 0.06, 3.45 ± 0.14 and 3.80 ± 0.05, n=5) but not the Kir subtype channel (pD2 = 4.15 ± 0.10, n=5). Cyclic nucleotides were not involved as the relaxation due to aminophylline (pD2 = 4.27 ± 0.09, n=5) was not altered in the presence of 3 × 10(-5) M trachylobane-318 (pD2 = 4.46 ± 0.08, n=5). Thus, at a functional level, trachylobane-318 seems to relax the guinea-pig trachea by positive modulation of K(+) channels, particularly the KATP, KV, SKCa and BKCa subtypes. </p>","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"49 ","pages":"15-25"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.49.15","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31205718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Non-genomic effects of progesterone on Rho kinase II in rat gastric smooth muscle cells.","authors":"Othman Al-Shboul, Ayman Mustafa, Farah Al-hashimi","doi":"10.1540/jsmr.49.55","DOIUrl":"https://doi.org/10.1540/jsmr.49.55","url":null,"abstract":"Various studies have shown that pregnancy is associated with gastrointestinal complaints that might result from disturbance of the normal contractile pattern of smooth muscle. Progesterone is an important steroid hormone, which plays a crucial role in female pregnancy. Progesterone affects muscle cells by genomic mechanisms, through nuclear receptors, and non-genomic mechanisms, through unidentified pathways. Non-genomic actions were defined as those occurring within 10 min of progesterone exposure. The aim of the present study was to investigate the non-genomic effect of progesterone on Rho kinase II activity in gastric smooth muscle. Single smooth muscle cells of the stomach obtained from Sprague Dawley rats were used. Dispersed gastric smooth muscle cells were treated with progesterone or acetylcholine (ACh) separately. Cells designated for progesterone treatment were incubated with 1 μM progesterone for 10 min. Rho kinase II expression and both basal and ACh-induced Rho kinase II activity were measured via specifically designed enzyme-linked immunosorbent assay (ELISA) and activity assay kits respectively in both control and progesterone-treated groups. Progesterone inhibited the ACh-induced, but not the basal, Rho kinase II activity in dispersed gastric smooth muscle cells without affecting its expression level. This study suggested that progesterone can rapidly affect the contractile activity of isolated gastric smooth muscle cells in rats via inhibition of the Rho kinase II pathway.","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"49 ","pages":"55-62"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/28/07/jsmr-49-055.PMC5137272.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31813946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}