Detection of functional receptors for the proteinase-activated-receptor-2-activating polypeptide, SLIGRL-NH2, in rat vascular and gastric smooth muscle

1995 ◽  
Vol 73 (8) ◽  
pp. 1203-1207 ◽  
Author(s):  
Bahjaf Al-Ani ◽  
Mahmoud Saifeddine ◽  
Morley D. Hollenberg
Keyword(s):  
Smooth Muscle ◽  
Longitudinal Muscle ◽  
Rat Aorta ◽  
Peptide Sequence ◽  
Nitric Oxide Synthase Inhibitor ◽  
Aorta Ring ◽  
Gastric Smooth Muscle ◽  
Low Concentrations ◽  
The One ◽  
Synthase Inhibitor

We have studied the actions of the proteinase-activated-receptor-2 (PAR2)-activating polypeptide, SLIGRL-NH2 (SLI-NH2), in rat aorta and in gastric longitudinal muscle preparations. In the phenylephrine-precontracted aorta preparation, SLI-NH2 caused an endothelium-dependent relaxation that mimicked the action of low concentrations (0.5 U/mL) of trypsin and that was blocked by the nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester. In endothelium-free aorta ring preparations, SLI-NH2 caused neither a relaxation nor a contraction. In the gastric longitudinal muscle preparation, SLI-NH2 caused a transient contraction that mimicked the action of trypsin (0.5 U/mL) and that was sensitive to inhibitors of cyclooxygenase (indomethacin) and tyrosine kinase (genistein). Further, using a reverse-transcriptase – polymerase chain reaction (RT–PCR) approach we detected, in both assay tissues, mRNA for the rat PAR2 receptor, and we ascertained, using a cloned receptor cDNA obtained from a rat intestinal cDNA library, that the putative N-terminal activating peptide sequence of the rat PAR2 receptor (SLIGRL) is identical with the one previously cloned from murine tissue. We concluded that, like the thrombin receptor, the PAR2 receptor may play a pathophysiologic role in the regulation of vascular and gastric smooth muscle contractility.Key words: thrombin, proteinase-activated receptor 2, protease, smooth muscle.

Proteinase-activated receptor 4 (PAR4): action of PAR4-activating peptides in vascular and gastric tissue and lack of cross-reactivity with PAR1 and PAR2

1999 ◽  
Vol 77 (6) ◽  
pp. 458-464 ◽  
Author(s):  
Morley D Hollenberg ◽  
Mahmoud Saifeddine ◽  
Bahjat Al-Ani ◽  
Yu Gui
Keyword(s):  
Smooth Muscle ◽  
Longitudinal Muscle ◽  
Contractile Response ◽  
Calcium Signalling ◽  
Rat Aorta ◽  
Cross Reactivity ◽  
Relaxant Effect ◽  
Gastric Smooth Muscle ◽  
Proteinase Activated Receptors

We studied the actions of the human and murine proteinase-activated receptor 4 (PAR4) derived receptor-activating peptides (APs), GYPGQV-NH2 (GQV-NH2) and GYPGKF-NH2 (GKF-NH2), (i) to activate-desensitize either PAR1 or PAR2 in cultured cell systems (calcium signalling in PAR1/PAR2-bearing human HEK cells and in rat KNRK cells expressing either rat or human PAR2) and (ii) to affect contractility in rat aorta (RA) and rat gastric longitudinal muscle (LM) preparations in vitro. We found that neither PAR1 nor PAR2 was affected by concentrations of the PAR4-APs (800 µM) that caused both an endothelium-dependent nitric oxide mediated relaxation of preconstricted RA tissue and a contractile response in the LM preparation. The potencies (EC50 values 300 to 400 µM) of GQV-NH2 and GKF-NH2 for causing a relaxant effect were identical and comparable with the potency of GQV-NH2 for causing a contractile effect in the LM. However, the potencies of the PAR4-APs in the RA and LM preparations were 20- to 150-fold lower than the potency of the receptor-selective PAR1-AP, TFLLR-NH2. We conclude that the PAR4-APs do not activate either PAR1 or PAR2, and we suggest that along with PAR1 and PAR2, PAR4 may also be present in rat vascular and gastric smooth muscle.Key words: proteinase-activated receptors, PAR4, calcium, vascular smooth muscle, gastric smooth muscle, thrombin.

Stereoselective Differences in the Vasorelaxing Effects of S(+) and R(-) Ketamine on Rat Isolated Aorta 

1998 ◽  
Vol 88 (3) ◽  
pp. 718-724 ◽  
Author(s):  
Adriani Kanellopoulos ◽  
Gunther Lenz ◽  
Bernd Muhlbauer
Keyword(s):  
Nitric Oxide ◽  
Adenosine Triphosphate ◽  
Blocking Agent ◽  
Rat Aorta ◽  
K Channel ◽  
Nitric Oxide Synthase Inhibitor ◽  
Nitric Oxide Release ◽  
Racemic Ketamine ◽  
Synthase Inhibitor

Background S(+) ketamine, because of its higher anesthetic potency and lower risk of psychotomimetic reactions, has been suggested to be superior to presently available racemic ketamine. The racemate is a direct vasodilator in vivo, and thus the authors investigated the vasorelaxing effects of ketamine enantiomers on rat aorta. Methods Rat isolated aortic rings with and without endothelium were contracted with 3 x 10(-7) M norepinephrine. Then 10(-5) to 3 x 10(-3) M S(+), R(-), or racemic ketamine were added cumulatively. Vascular responses to ketamine were further studied in rings pretreated with the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (NNLA), the adenosine triphosphate-sensitive K+ channel antagonist glibenclamide, and the L-type calcium channel blocking agent D888. Results Ketamine enantiomers and the racemate produced concentration-dependent vasorelaxation. The relaxing effect of S(+) ketamine was significantly weaker compared with R(-) ketamine and the racemate reflected by the half-maximum effective concentration (EC50) values of 11.6 x 10(-4), 4.8 x 10(-4), and 6 x 10(-4) M, respectively. Removal of the endothelium and NNLA or glibenclamide pretreatment did not significantly alter the vasorelaxing effect of ketamine. In contrast, D888 pretreatment significantly shifted the concentration-effect curves of both S(+) and R(-) ketamine rightward (EC50 values of 18.9 x 10(-4) and 8.5 x 10(-4) M, respectively), whereas the difference between the isomers was not affected. Conclusions Vasorelaxation by ketamine enantiomers is quantitatively stereoselective: The effect of S(+)ketamine is significantly weaker compared with that of the racemate and R(-) ketamine. This stereoselective difference is not due to nitric oxide release, activation of adenosine triphosphate-sensitive potassium channels, or differential inhibition of L-type calcium channels.

Vasoconstrictive effect of hydrogen sulfide involves downregulation of cAMP in vascular smooth muscle cells

2008 ◽  
Vol 295 (5) ◽  
pp. C1261-C1270 ◽  
Author(s):  
Jia Jia Lim ◽  
Yi-Hong Liu ◽  
Ester Sandar Win Khin ◽  
Jin-Song Bian
Keyword(s):  
Smooth Muscle ◽  
Hydrogen Sulfide ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Nitric Oxide Synthase Inhibitor ◽  
Vasorelaxant Effect ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Hydrogen sulfide (H2S), a new endogenous mediator, produces both vasorelaxation and vasoconstriction. This study was designed to examine whether cAMP mediates the vasoconstrictive effect of H2S. We found that NaHS at a concentration range of 10–100 μM (yields ∼3–30 μM H2S) concentration-dependently reversed the vasodilation caused by isoprenaline and salbutamol, two β-adrenoceptor agonists, and forskolin, a selective adenylyl cyclase activator, in phenylephrine-precontracted rat aortic rings. Pretreatment with NaHS (10–100 μM) for 5 min also significantly attenuated the vasorelaxant effect of salbutamol and forskolin. More importantly, NaHS (5–100 μM) significantly reversed forskolin-induced cAMP accumulation in vascular smooth muscle cells. However, NaHS produced significant, but weaker, vasoconstriction in the presence of NG-nitro-l-arginine methyl ester (100 μM), a nitric oxide synthase inhibitor, or in endothelium-denuded aortic rings. Blockade of ATP-sensitive potassium channels with glibenclamide (10 μM) failed to attenuate the vasoconstriction induced by H2S. Taken together, we demonstrated for the first time that the vasoconstrictive effect of H2S involves the adenyly cyclase/cAMP pathway.

scholarly journals Features of the bradykinin-induced contraction of the gastric smooth muscle depending on the concentration of compounds based on 3-substituted-1,4-benzodiazepin-2-ones

2016 ◽  
Vol 21 (2) ◽  
pp. 19-23
Author(s):  
P. Virych ◽  
O. Shelyuk ◽  
V. Martynyuk ◽  
V. Pavlovsky
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Contractile Activity ◽  
Smooth Muscles ◽  
Competitive Inhibitor ◽  
Smooth Muscle Contraction ◽  
Gastric Smooth Muscle ◽  
Low Concentrations

The effect of compounds based on 3-substituted-1,4-benzodiazepine-2-ones on contractile activity of smooth muscles of the rat's stomach was analyzed. Action substances MX-1626, MX-1775 for the smooth muscle contraction of like competitive inhibitor of bradykinin – des-Arg9- [Leu8]-Bradykinin acetate, which is observed as increase normalized rate of contraction with increasing of bradykinin concentration and characterized by a slowdown in the first phase of contraction. The most effective 3-subtituted 1,4-benzodiazepin-2-ones was at low concentrations of bradykinin, increasing it concentration their effect is reduced.

scholarly journals Changes in Gastric Smooth Muscle Cell Contraction during Pregnancy: Effect of Estrogen

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Othman A. Al-Shboul ◽  
Hanan J. Al-Rshoud ◽  
Ahmed N. Al-Dwairi ◽  
Mohammad A. Alqudah ◽  
Mahmoud A. Alfaqih ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Late Pregnancy ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Enzyme Linked Immunosorbent Assay ◽  
Sprague Dawley ◽  
Gastric Smooth Muscle ◽  
Sprague Dawley Rats ◽  
Polymerase Chain ◽  
Synthase Inhibitor

It is well known that pregnancy is associated with frequent gastrointestinal (GI) disorders and symptoms. Moreover, previous reports have shown that estrogen, which changes in levels during pregnancy, participates in the regulation of GI motility and is involved in the pathogenesis of various functional disorders in the stomach. The aim of the current study was to explore the changes in the expression of estrogen receptors (ERs) and examine the effect of estrogen on nitric oxide- (NO-) cyclic guanosine monophosphate (cGMP) pathway and thus relaxation in gastric smooth muscle cells (GSMC) during pregnancy. Single GSMC from early-pregnant and late-pregnant Sprague-Dawley rats were used. Protein and mRNA expression levels of ERs were measured via specifically designed enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR), respectively. NO and cGMP levels were measured via specifically designed ELISA kits. Effect of estrogen on acetylcholine- (ACh-) induced contraction of single GSMC was measured via scanning micrometry in the presence or absence of the NO synthase inhibitor,N-nitro-L-arginine (L-NNA), or guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ). Estrogen increased both NO and cGMP levels and their levels were greater in early compared to late pregnancy. Expression of ERs was greater in early compared to late pregnancy. ACh induced greater contraction of GSMC in late pregnancy compared to early pregnancy. Estrogen inhibited ACh-induced contraction in both periods of pregnancy. Importantly, pretreatment of GSMC with either L-NNA or ODQ abolished estrogen inhibitory action on muscle contraction. In conclusion, GSMC contractile behavior undergoes drastic changes in response to estrogen during pregnancy and this might explain some of the pregnancy-associated gastric disorders.

Gender differences in the endothelial regulation of α2-adrenoceptor-mediated contraction in the rat aorta

1999 ◽  
Vol 97 (1) ◽  
pp. 19-25 ◽  
Author(s):  
Nuria TEJERA ◽  
Gloria BALFAGÓN ◽  
Jesús MARÍN ◽  
Mercedes FERRER
Keyword(s):  
Rank Order ◽  
Rat Aorta ◽  
Ovariectomized Rats ◽  
Maximal Response ◽  
Nitric Oxide Synthase Inhibitor ◽  
Adrenoceptor Antagonist ◽  
Α2 Adrenoceptor ◽  
No Release ◽  
Synthase Inhibitor ◽  
Oxide Synthase

The aim of this study was to determine the possible influence of sex hormones on the contractile responses induced by clonidine, an agonist of α2-adrenoceptors, as well as the endothelial modulation of these responses. For this purpose, thoracic aorta segments from male (control and castrated) and female (in oestrous phase and ovariectomized) rats were used. In intact segments from the four groups of rats, clonidine (0.01-10 µmol/l) induced concentration-dependent contractions, which were increased by the nitric oxide synthase inhibitor Nω-nitro-⌊-arginine methyl ester (0.1 mmol/l) or by endothelium removal, but were reduced by 1 µmol/l yohimbine (an α2-adrenoceptor antagonist) in all animals and by 1 µmol/l indomethacin (a cyclo-oxygenase inhibitor) in control males only. The rank order of the magnitude of the maximal response was: oestrous females > ovariectomized females > control males > castrated males, whereas the sensitivity to clonidine (EC50 value) was similar in all animals. In endothelium-denuded segments, the rank order was: oestrous females = control males > ovariectomized females = castrated males. These results suggest that: (1) the presence of oestrogen or androgen increases the contraction caused by α2-adrenoceptor activation with clonidine; (2) endothelium negatively modulates the response to this agonist in the four groups of rats, due to endothelial NO release (entirely in females and in part in males); (3) androgen also seems to modulate the response by stimulating the release of an endothelial contracting factor, probably a prostanoid; and (4) the endothelium of males has a greater capacity than that of comparable females for negative regulation of the tension generated by the underlying vascular smooth muscle.

scholarly journals Ca2+ influx mediates enhanced α2-adrenergic contraction in aortas from rats treated with NOS inhibitor

2001 ◽  
Vol 281 (5) ◽  
pp. H2233-H2240 ◽  
Author(s):  
Harshini Mukundan ◽  
Nancy L. Kanagy
Keyword(s):  
Calcium Imaging ◽  
Rat Aorta ◽  
Nitric Oxide Synthase Inhibitor ◽  
Voltage Dependent Calcium Channel ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
Nos Inhibitor ◽  
The Common ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Previously, we reported that aortic segments from rats made hypertensive with the nitric oxide synthase inhibitor N ω-nitro-l-arginine (l-NNA) exhibit enhanced contractile sensitivity to both α2-adrenergic receptor (α2-AR) stimulation and to KCl-induced depolarization. We hypothesized that increased contractile responses to these agents was due to a change in the common effector L-type voltage-dependent calcium channel (VDCC). In aortic segments from control and l-NNA-treated rats, contraction to the α2-AR agonist UK-14304 stimulated Ca2+influx but released intracellular Ca2+ only in control arteries. UK-14304-induced contraction was blocked by the VDCC antagonist nifedipine in both control and l-NNA aortas but contraction of aortas from l-NNA-treated rats was blocked by lower concentrations. Calcium imaging studies in fura 2-loaded freshly isolated aortic vascular smooth muscle cells also demonstrated UK-14304-stimulated Ca2+ influx sensitive to nifedipine only in cells from l-NNA-treated rats. We conclude that α2-AR contraction in the rat aorta is mediated primarily by Ca2+ influx and that l-NNA-induced hypertension increases the dependence of this contraction on VDCCs.

Acrolein-induced vasomotor responses of rat aorta

2003 ◽  
Vol 285 (2) ◽  
pp. H727-H734 ◽  
Author(s):  
Nina L. Tsakadze ◽  
Sanjay Srivastava ◽  
Sunday O. Awe ◽  
Ayotunde S. O. Adeagbo ◽  
Aruni Bhatnagar ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Rat Aorta ◽  
Nitric Oxide Synthase Inhibitor ◽  
Vasomotor Responses ◽  
Endothelial Denudation ◽  
Synthase Inhibitor ◽  
Resting Tone ◽  
Oxide Synthase ◽  
Dose Dependent

Acrolein is a highly reactive aldehyde pollutant and an endogenous product of lipid peroxidation. Increased generation of, or exposures to, acrolein incites pulmonary and vascular injury. The effects of acrolein on the vasomotor responses of rat aortic rings were studied to understand its mechanism of action. Incubation with acrolein (10–100 μM) alone did not affect the resting tone of aortic vessels; however, a dose-dependent relaxation of phenylephrine-precontracted aortic rings was observed. Acrolein-induced relaxation was slow and time dependent and the extent of relaxation after 100 min of application was 44.7 ± 4.1% (10 μM), 56.0 ± 5.6% (20 μM), 61.0 ± 7.9% (40 μM), and 96.1 ± 2.1 (80 μM), respectively, versus 14.2 ± 3.3% relaxation in the absence of acrolein. Acrolein-induced vasorelaxation was prevented by endothelial denudation and was abolished on pretreatment with the nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester, the guanylyl cyclase inhibitor 1 H-[1,2,4]oxidazolo[4,3- a]quinoxaline-1-one, or the cyclooxygenase inhibitor indomethacin. Inhibition of K+ channels (by tetrabutylammonium) or Na+-K+-ATPase (by ouabain) did not significantly prevent acrolein-mediated vasorelaxation. Exposure to acrolein in the presence or absence of other compounds elicited slow wave vasomotor effect in 77% of aortic vessels versus 1.4% in control. Vasomotor responses were also studied on aortic rings prepared from rats fed 2 mg · kg–1 · day–1 acrolein for 3 alternate days by oral gavage. These vessels developed a significantly lower contractile response to phenylephrine compared with controls. Together, these results indicate that acute acrolein exposure evokes delayed vasorelaxation due to a nitric oxide- and prostacyclin-dependent mechanism, whereas in vivo acrolein exposure compromises vessel contractility.

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