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.

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.

Levobupivacaine-induced contraction of isolated rat aorta is calcium dependent

2011 ◽  
Vol 89 (7) ◽  
pp. 467-476 ◽  
Author(s):  
Ji Seok Baik ◽  
Ju-Tae Sohn ◽  
Seong-Ho Ok ◽  
Jae-Gak Kim ◽  
Hui-Jin Sung ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Smooth Muscle ◽  
Calcium Influx ◽  
Rat Aorta ◽  
Isometric Tension ◽  
Guanosine Monophosphate ◽  
Response Curves ◽  
Calcium Dependent ◽  
Isolated Rat

Levobupivacaine is a long-acting local anesthetic that intrinsically produces vasoconstriction in isolated vessels. The goals of this study were to investigate the calcium-dependent mechanism underlying levobupivacaine-induced contraction of isolated rat aorta in vitro and to elucidate the pathway responsible for the endothelium-dependent attenuation of levobupivacaine-induced contraction. Isolated rat aortic rings were suspended to record isometric tension. Cumulative levobupivacaine concentration–response curves were generated in either the presence or absence of the antagonists verapamil, nifedipine, SKF-96365, 2-aminoethoxydiphenylborate, Gd3+, NW-nitro-l-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), and methylene blue, either alone or in combination. Verapamil, nifedipine, SKF-96365, 2-aminoethoxydiphenylborate, low calcium concentrations, and calcium-free Krebs solution attenuated levobupivacaine-induced contraction. Gd3+ had no effect on levobupivacaine-induced contraction. Levobupivacaine increased intracellular calcium levels in vascular smooth muscle cells. L-NAME, ODQ, and methylene blue increased levobupivacaine-induced contraction in endothelium-intact aorta. SKF-96365 attenuated calcium-induced contraction in a previously calcium-free isotonic depolarizing solution containing 100 mmol/L KCl. Levobupivacaine-induced contraction of rat aortic smooth muscle is mediated primarily by calcium influx from the extracellular space mainly via voltage-operated calcium channels and, in part, by inositol 1,4,5-trisphosphate receptor-mediated release of calcium from the sarcoplasmic reticulum. The nitric oxide – cyclic guanosine monophosphate pathway is involved in the endothelium-dependent attenuation of levobupivacaine-induced contraction.

scholarly journals INHIBITORY EFFECT OF ETHANOLIC EXTRACT OF ERIOBOTRYA JAPONICA LEAVES PRE-INCUBATED WITH THEOPHYLLINE AND ASPIRIN ON ISOLATED GUINEA PIG TRACHEAL

2018 ◽  
Vol 11 (13) ◽  
pp. 46
Author(s):  
Marianne Marianne ◽  
Urip Harahap ◽  
Emil Salim ◽  
Dadang Irfan Husori ◽  
Fahrumsyah Jali Rambe ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Protective Effect ◽  
Contractile Response ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
Inhibitory Effect ◽  
Eriobotrya Japonica ◽  
Relaxant Effect ◽  
Significant Difference

 Objectives: The objectives of the study were to examine the inhibitory effect of ethanol extract of Eriobotrya japonica leaves (EEEJL) pre-incubated with theophylline and aspirin on isolated guinea pig tracheal chains against acetylcholine (ACh)-induced contraction.Methods: The effect of EEEJL (1-8 mg/Ml) on the isolated tracheal strips was tested in vitro. Furthermore, the mechanism of relaxant effects of EEEJL was evaluated in the presence of theophylline and aspirin.Results: The contractile response evoked by Ach (1.25 × 10−3 M) was decreased by EEEJL (effective concentration50 = 1.36 mg/mL) and has no significant difference of relaxant effect to that of EEEJL pre-incubated with theophylline and aspirin (p>0.05).Conclusion: The EEEJL decreased the ACh-induced contraction through the inhibition of PDE and the protective effect on prostaglandin E2.

Increased responsiveness of jejunal longitudinal muscle in Trichinella-infected rats

1988 ◽  
Vol 254 (1) ◽  
pp. G124-G129 ◽  
Author(s):  
D. L. Vermillion ◽  
S. M. Collins
Keyword(s):  
Smooth Muscle ◽  
Muscle Function ◽  
Longitudinal Muscle ◽  
Trichinella Spiralis ◽  
Passive Tension ◽  
Active Tension ◽  
Maximum Tension ◽  
Longitudinal Smooth Muscle ◽  
Smooth Muscle Function

We examined in vitro changes in contractility of jejunal longitudinal muscle strips in rats infected with the nematode parasite Trichinella spiralis. Length-passive tension relationships were unchanged. However, muscle from infected rats on days 5 and 6 postinfection (PI) generated maximal active tension induced by carbachol at significantly less stretch (39.9 +/- 1.0 and 34.3 +/- 6.3%, respectively) than control tissues (66.0 +/- 2.3%). In infected rats on day 5 PI, the maximum tension generated by carbachol (1.6 +/- 0.4 g/mm2) and by 5-hydroxytryptamine (5-HTP) (2.6 +/- 0.1 g/mm2) was significantly greater than in control tissue (0.5 +/- 0.2 g/mm2). On removal of calcium from the medium, responses of muscle from control and infected rats were reduced in a proportionate manner. The increased responsiveness to carbachol and 5-HTP was maximal by day 5 PI and was associated with a decrease in the ED50 value for 5-HTP but not for carbachol. All changes were reversed by 23 days PI. These results indicate that T. spiralis infection in the rat is associated with alterations in jejunal longitudinal smooth muscle function.

Effects of cholecystokinin-octapeptide on gastric motility of anesthetized dogs

1986 ◽  
Vol 251 (5) ◽  
pp. G678-G681 ◽  
Author(s):  
A. Kuwahara ◽  
K. Ozawa ◽  
N. Yanaihara
Keyword(s):  
Smooth Muscle ◽  
Gastric Motility ◽  
Contractile Response ◽  
Smooth Muscle Contraction ◽  
Dependent Manner ◽  
Local Effects ◽  
Cholecystokinin Octapeptide ◽  
Gastric Smooth Muscle ◽  
Anesthetized Dogs ◽  
Dose Dependent

The present experiments examined the local effects of cholecystokinin-octapeptide (CCK-8) and related peptides on gastric motility of anesthetized dogs. Peptides were injected through the gastroepiploic artery at doses of 1.0, 2.5, 5.0, 10.0, and 20.0 ng/ml. CCK-8 and its analogues (Glt-CCK-8, pGlu-CCK-8, and Suc1-MePhe8-CCK-7) increased gastric smooth muscle contraction in a dose-dependent manner. ED50 of CCK-8 was 2.97 +/- 0.63 ng/ml. Administration of atropine (100–200 micrograms/kg) inhibited the effects of both CCK-8 and pentagastrin; however, hexamethonium (5 mg/kg) failed to block the contractile response induced by CCK-8 and pentagastrin. These results indicate that CCK-8 and related peptides can act as local modulators in controlling the neural regulation of gastric motility.

T-2 toxin effect on rat aorta: Cellular changes in vivo and growth of smooth muscle cells in vitro

1987 ◽  
Vol 47 (2) ◽  
pp. 143-153 ◽  
Author(s):  
R. Yarom ◽  
Y. Sherman ◽  
F. Bergmann ◽  
A. Sintov ◽  
L.D. Berman
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Rat Aorta ◽  
Cellular Changes

In vitro microelectrode study of the electrical properties of smooth muscle in equine ileum

2001 ◽  
Vol 149 (23) ◽  
pp. 707-711 ◽  
Author(s):  
N. P. H. Hudson ◽  
I. G. Mayhew ◽  
G. T. Pearson
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Smooth Muscle Cells ◽  
Longitudinal Muscle ◽  
Muscle Cells ◽  
Muscle Layer ◽  
Potential Oscillations ◽  
Longitudinal Muscle Layer ◽  
Membrane Potential Oscillations

Intracellular microelectrode recordings were made from smooth muscle cells in cross-sectional preparations of equine ileum, superfused in vitro. Membrane potential oscillations and spike potentials were recorded in all preparations, but recordings were made more readily from cells in the longitudinal muscle layer than from cells in the circular layer. The mean (se) resting membrane potential (RMP) of smooth muscle cells in the longitudinal muscle layer was -51.9 (1.2) mV, and the membrane potential oscillations in this layer had a mean amplitude of 4.8 (0.4) mV, a frequency of 9.0 (0.1) cycles per minute and a duration of 5.8 (0.2) seconds. The membrane potential oscillations were preserved in the presence of tetrodotoxin. A waxing and waning pattern of membrane potential oscillation activity was observed. Nifedipine abolished the spiking contractile activity of the smooth muscle, did not abolish the membrane potential oscillations but did alter their temporal characteristics.

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