SEARCH · PubMed Health

Results for “SPASMOLYTICS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources

PubMed1991

Spasmolytic effect of cromakalim in dog coronary artery in vitro.

Isometric force development was measured in isolated ring segments of dog left anterior descending coronary artery to K+ (10-70 mM), U-46619 (0.3-30 nM), endothelin-1 (0.1-30 nM), 5-HT (0.1-30 microM) and angiotensin-II (0.1-30 nM). Compared with the maximum tissue response to a K+ depolarizing solution (100%) there was a marked variation in the maximum response to each spasmogen: K+ (111%), U-46619 (85%), endothelin-1 (48%), 5-HT (49%) and angiotensin-II (15%). In arteries pretreated with cromakalim (0.3 - 10 microM) the maximum response to all constrictor agents (with the exception of K+) was reduced but the potency was unaffected. Maximum responses to angiotensin-II and 5-HT were affected at concentrations approximately threefold lower than those to endothelin-1 and U-46619. Removal of the endothelium increased the maximum response caused by 5-HT and reduced the potency of cromakalim in inhibiting this contraction. Glyceryl trinitrate and sodium nitroprusside were 100-1000 times more potent than cromakalim although they produced qualitatively similar effects. Cromakalim is an effective spasmolytic against a number of vasoconstrictors in the dog coronary artery. No marked spasmogen selectivity could be identified for cromakalim that was not shown by glyceryl trinitrate or sodium nitroprusside.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1992

Immunohistochemical localization of pancreatic spasmolytic polypeptide (PSP) in the pig.

Pancreatic spasmolytic polypeptide (PSP) is a peptide that is isolated from the porcine pancreas and that affects intestinal motility and growth of intestinal tumour cells in vitro. The peptide was recently demonstrated to be present in large amounts in pancreatic juice. The cellular origin of the peptide, however, is largely unclarified and the localization was therefore studied of PSP in pigs using immunohistochemistry. Positive immunoreactions were seen in the pancreas, the stomach, the duodenum, the jejunum and the ileum. In the pancreas, the PSP immunoreaction was seen in all acinar cells; no immunoreaction was seen in the endocrine islets. In the stomach, it was localized to the mucous cells of the glands in the cardiac gland region, the corpus and the pylorus. In the duodenum a strong immunoreaction was present in Brunner's glands and in the cells of their excretory ducts. In the jejunum and ileum, PSP immunoreactivity was seen in some of the cells in the epithelium of the crypts of Lieberkühn. A peptide chromatographically identical to highly purified PSP was identified in pancreas and stomach extracts. Thus epithelial cells in all parts of the stomach and small intestine contribute to the supply of PSP to the gut lumen.

Animals↗

PubMed1990

Effects of HA1077, a novel calciumantagonistic spasmolytic agent on intracerebral arterioles of rats.

The effects of the new spasmolytic agent HA1077, which belongs to the calciumantagonists but acts by mechanisms different from those of conventional calcium channel blockers, on the cerebral microcirculation were studied in rats using isolated and cannulated intracerebral (parenchymal) arterioles of 50 microns average diameter. After the vessels had developed spontaneous tone, increasing concentrations of HA1077 were applied extraluminally. HA1077 induced vasodilation in a dose-dependent manner with a maximal increase of vessel diameter of 73.9 +/- 5.1% (mean +/- SEM, n = 5) at 10(-4) M and with half-maximal responses (ED50) of 1.00 x 10(-6) M. The extent of maximal vasodilation achieved by HA1077 was significantly greater than that induced by such conventional calcium channel blockers as diltiazem, verapamil, nifedipine and nimodipine (about 50% each in a previous report from our laboratory). Vasoconstriction induced by synthetic thromboxane A2 (10(-9) M to 10(-5) M) which is through to be highly dependent on intracellular calcium, was completely inhibited by 10(-4) M HA1077, whereas both verapamil and nimodipine at a concentration at maximal vasodilation effects (10(-5) M and 10(-7) M respectively) only partially inhibited such vasoconstriction. These results suggest that HA1077 may exert a more potent vasodilator effect on the cerebral microcirculation than do conventional calcium channel blockers.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1983

Spasmolytic activity of the flavonoids from Thymus vulgaris.

Flavonoids from Thymus vulgaris L. have been studied in vitro for spasmolytic activity on the smooth muscles of the guinea-pig ileum and trachea and of the rat vas deferens. The flavones and thyme extracts inhibit responses to agonists which stimulate specific receptors (acetylcholine, histamine, L-noradrenaline) as well as to agents whose actions are not mediated via specific receptors (BaCl2). Cumulative dose-response curves point to a non-competitive antagonism. Inhibition of Ca2+ contractions on K+ depolarized smooth muscles suggest inhibition of availability of Ca2+ for muscle contraction. pD'2 values were determined to compare the potency of these components to each other and to standard drugs. Flavones induce relaxation of the carbachol contracted tracheal strip without stimulation of the beta 2-receptors, which were blocked by propranolol.

Animals↗

PubMed1996

Influence of spasmolytic analgesics on motility of sphincter of Oddi.

The effects on the sphincter of Oddi of intravenous administration of dipyrone, 2.5 g; tramadol, 50 mg; indomethacin, 75 mg; N-butylscopolamine, 20 mg; and nitroglycerin, 1 mg, in comparison to physiological saline were assessed in a single-blind study in 36 patients hospitalized with upper abdominal pain. Basal sphincter pressure and sphincter motility were measured for a 5-min period after treatment by endoscopic manometry. Nitroglycerin and dipyrone both caused a significant fall in basal sphincter pressure, while N-butylscopolamine and nitroglycerin produced a significant decrease in contraction frequency. Therefore, dipyrone, in contrast to tramadol and indomethacin, exhibits spasmolytic activity in addition to analgesia in biliary pain.

Analgesics, Opioid↗

PubMed1997

Close physical linkage of the genes encoding the pNR-2/pS2 protein and human spasmolytic protein (hSP).

Trefoil proteins contain a conserved domain of distinctive structure. Three human trefoil proteins have been described to date of which the human spasmolytic polypeptide (hSP) and pNR-2/pS2 proteins have a similar pattern of expression in normal tissues. The genes encoding these two proteins were isolated from a human DNA library. Preliminary experiments suggested that some recombinants contained both genes. Southern hybridisation showed that all the recombinants were derived from a single stretch of DNA spanning 45 kb and suggested that the hSP gene was located downstream of the pNR-2/pS2 gene. Further experiments demonstrated that the two genes are transcribed in the same direction and that the distance between the 3' end of the pNR-2/pS2 gene and the 5' end of the hSP gene is 12.5 kb. The close linkage of these two genes is evidence that they have evolved by gene duplication and that their similar pattern of expression in normal tissues could result from the retention of common regulatory elements.

Chromosomes, Human, Pair 21↗

PubMed1978

Biliary spasmolytic action of 3-(2,4,5-triethoxybenzoyl)propionic acid (AA-149) in dogs.

The spasmolytic action of 3-(2,4,5-triethoxybenzoyl)propionic acid (AA-149) on the biliary tract was investigated in anesthetized dogs. Intravenous administration of AA-149 at 2 mg/kg and higher doses produced a dose-dependent reduction in passage resistance through the choledochoduodenal junction and in gallbladder pressure, and a dose-dependent increase in bile flow. AA-149, like cholecystokinin, decreased biliary ductal pressure in spite of increasing the bile flow in dogs with ligation of the cystic duct of the gallbladder, whereas taurocholate increased the pressure as well as the bile flow. Moreover, the spasmic response of the choledochoduodenal junction to morphine was depressed strongly by AA-149, BUT NOT CONSISTENTLY BY ATROPINE. The effects of AA-149 were not influenced by pretreatment with atropine, phentolamine or propranolol. These findings strongly suggest that AA-149 relaxed the biliary tract and depressed the morphine-induced spasm by a mechanism different from those of anticholinergic and sympathomimetic agents.

Animals↗

PubMed1983

Effects of spasmolytics on K+-induced contraction of rat intestine in vivo.

Eight spasmolytic drugs commonly used in the treatment of the irritable bowel syndrome were compared to verapamil with respect to their effects (all drugs injected i.v.) on the contraction of duodenum, ileum and colon induced by high K+ topical application in the anaesthetized rat. Verapamil greater than rociverine greater than papaverine greater than mebeverine greater than dicyclomine antagonized dose-dependently the contraction of duodenum and colon, the activity on duodenum being from 2 (rociverine) to 10 (verapamil) fold higher. Verapamil and rociverine, but not the other drugs mentioned above, were also active on ileum. N-Butylscopolammonium bromide, phloroglucinol and trimebutine were inactive against the contraction of the three intestinal tracts and prifinium bromide was inactive on duodenum and ileum, while it had remarkable activity on colon, unrelated to its antimuscarinic activity. The results are discussed briefly with reference to the pharmacological therapy of the irritable bowel syndrome.

Animals↗

PubMed1987

Different spasmolytic effects of smooth muscle relaxants on the guinea-pig esophageal muscularis mucosae contracted by carbachol or high potassium in vitro.

The responsiveness of the guinea-pig esophageal muscularis mucosae to smooth muscle relaxants was examined in vitro during the contractile state induced by carbachol (3 microM) or high potassium (60 mM). In the presence of phentolamine (3 microM), all catecholamines tested (10 nM-30 microM) relaxed the carbachol-induced tone more effectively than the high potassium-induced tone, and the maximum relaxations reached about 90-95% for carbachol but only about 40% for high potassium. Verapamil produced a concentration-dependent relaxation of the muscularis mucosae precontracted with either spasmogen; the mean EC50 values (-log M) were 6.73 for high potassium and 4.65 for carbachol. Methylene blue (1-300 microM) relaxed the carbachol-contracted muscularis mucosae in a concentration-dependent manner but relaxed the high potassium-contracted one less potently. Forskolin (1-300 microM), papaverine (1-100 microM), aminophylline (10-300 microM), trifluoperazine (1-300 microM), 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (10-300 microM), quinacrine (1-300 microM) and dibutyryl cyclic AMP (100 microM-3 mM) produced relaxation almost equipotently in both contractile states whereas adenosine (10 microM-1 mM), sodium nitroprusside (10-300 microM) and dibutyryl cyclic GMP (100 microM-3 mM) were virtually ineffective. The present results indicate that a variety of smooth muscle relaxants have different spasmolytic effects on the guinea-pig isolated esophageal muscularis mucosae which was precontracted with carbachol or high potassium and that catecholamines and methylene blue may produce relaxation independent of the changes in intracellular cyclic nucleotides, calmodulin or phosphoinositides.

Animals↗

PubMed1989

A new family of growth factor-like peptides. 'Trefoil' disulphide loop structures as a common feature in breast cancer associated peptide (pS2), pancreatic spasmolytic polypeptide (PSP), and frog skin peptides (spasmolysins).

Four peptides present in completely different biological sources have been shown to exhibit a large degree of structural similarity. The peptides include: (i) a 60 amino acid residue breast cancer associated pS2 peptide isolated from human gastric juice and the culture media of the human breast cancer cell line MCF-7; (ii) a 106 amino acid residue pancreatic spasmolytic polypeptide (PSP) isolated from porcine pancreas and pancreatic juice; and (iii) a 49 and 50 amino acid residue peptide predicted from a cDNA isolated from the skin of the frog, Xenopus laevis. These peptides are characterized by having one (pS2 and the frog peptides) or two (PSP) domains of a highly conserved 38-39 amino acid residue consensus sequence not found in any other known peptides or proteins. The domain sequences contain 6 cysteine residues in nearly the same positions and it is suggested that these 6 residues are linked by 3 disulphide bonds to form a characteristic 'trefoil' disulphide loop structure common in all four peptides. From the sources of which the peptides have been isolated and from experiments showing that PSP has a growth factor stimulatory effect on MCF-7 cells, it is further suggested that these peptides may represent members of a new family of growth factors.

Amino Acid Sequence↗

PubMed1989

Growth stimulatory effect of pancreatic spasmolytic polypeptide on cultured colon and breast tumor cells.

The effects of a novel polypeptide, pancreatic spasmolytic polypeptide (PSP) on a colon carcinoma cell line (HCT 116) were examined. PSP stimulated the incorporation of [3H]thymidine into HCT 116 cells as well as cell proliferation in a dose-dependent manner. Maximal increase in [3H]thymidine incorporation of 50-60% occurred at 3-300 microM PSP. The VIP-mediated-increase in cAMP levels was reduced by PSP at greater than 1 microM concentrations. PSP is highly homologous to the estrogen-induced pS2 protein in MCF-7 breast cancer cells. We find that PSP also enhanced [3H]thymidine incorporation in MCF-7 cells. These findings indicate for the first time that PSP has growth stimulatory properties.

Animals↗

PubMed1993

Purification and characterization of the trefoil peptide human spasmolytic polypeptide (hSP) produced in yeast.

Recombinant human spasmolytic polypeptide (r-hSP) has been produced in relatively large amounts in Saccharomyces cerevisiae. The two intronless trefoil domains of the hSP-DNA were cloned separately by PCR from human genomic DNA, and the remaining parts of the gene synthesized. Recombinant plasmids were constructed to encode a fusion protein consisting of a hybrid leader sequence and the hSP sequence. The leader sequence serves to direct the fusion protein into the secretory pathway of the cell and to expose it to the Kex 2 processing enzyme system. The secreted r-hSP was found in a glycosylated and an non-glycosylated form. The two forms of r-hSP were purified from the yeast fermentation broth by a combination of ion-exchange chromatography and preparative HPLC. The overall yield from 8 litres of fermentation broth was 160 mg r-hSP and 219 mg glycosylated r-hSP corresponding to 50% and 34%, respectively. The structure of the r-hSP and the glycosylated r-hSP was determined by amino acid analysis and carbohydrate composition analysis as well as by peptide mapping, amino acid sequencing and mass spectrometric analysis.

Amino Acid Sequence↗

PubMed1994

Spasmolytic polypeptide: a trefoil peptide secreted by rat gastric mucous cells.

BACKGROUND/AIMS: Spasmolytic polypeptide (SP) is a trefoil peptide expressed in the digestive tract. This study aimed to determine the structure and distribution of SP expression in the rat gastrointestinal tract. METHODS: The structure of rat SP was determined from the sequence of complementary DNAs isolated from antral RNA. SP gene expression was localized by Northern blotting and in situ hybridization in the adult and fetal rat digestive tract. Expression of the SP peptide was localized by immunocytochemistry and Western blot analysis. RESULTS: SP messenger (m)RNA was found predominantly in the stomach with highest expression in the antrum. High levels of SP mRNA were expressed in the fetal stomach before gastrin and somatostatin expression. Surprisingly, SP mRNA and peptide did not colocalize in the gastric mucosa, SP mRNA being superficial to SP peptide immunoreactivity throughout the gastric mucosa. Abundant SP immunoreactivity was seen in the lumen of the gastric glands and the mucus layer adherent to the gastric mucosa, indicating luminal secretion. CONCLUSIONS: In the rat, SP is a peptide secreted predominantly from antral mucous cell. The high concentrations of SP in the adherent gastric mucus layer (approximately 10 mumol/L) suggest that SP functions as a structural peptide rather than a regulatory peptide.

Amino Acid Sequence↗

PubMed1992

Crystallization and preliminary X-ray diffraction studies of pancreatic spasmolytic polypeptide.

Pancreatic spasmolytic polypeptide (PSP) isolated from porcine pancreas has been crystallized by the hanging drop vapour diffusion method. The crystals belong to the space group I222 or I2(1)2(1)2(1) with cell dimensions a = 181.9 A, b = 54.5 A, c = 72.9 A. The crystals diffract to at least 2.5 A resolution and the asymmetric unit contains two molecules (Vm = 3.9 A3/Da) with a solvent content of 68% as determined by density measurements of the crystals. The self-rotation function suggests that the two molecules within the asymmetric unit are related by a 2-fold axis at either 30 degrees or 60 degrees from a in a plane perpendicular to the b axis.

Animals↗

PubMed1982

Pancreatic spasmolytic polypeptide (PSP): I. Preparation and initial chemical characterization of a new polypeptide from porcine pancreas.

A novel polypeptide, named Pancreatic Spasmolytic Polypeptide (PSP), was discovered in a side-fraction from the purification of porcine insulin. PSP was prepared by two different purification methods based on combinations of precipitations, anion-exchange and cation-exchange chromatography. The highest yield obtained, 52 mg PSP/kg pancreas, indicates that the content of PSP in porcine pancreas is about half the content of insulin. Both preparations appeared to be very pure as judged by basic disc electrophoresis, isoelectric focusing, analytical gel filtration and radioimmunoassays for various polypeptides known to be present in pancreas. The PSP molecule contains 106 amino acids (MW about 11 700). PSP is an acidic (pI 4.4), non-glycosylated protein without free N-terminal amino groups, and with high contents of proline and cystine. The high content of S-S bridges (7 per molecule), an unexpected low apparent MW determined by gel filtration, and a remarkable resistance towards treatment with trypsin and chymotrypsin, point to a compact structure of the PSP molecule.

Amino Acids↗

PubMed1982

Pancreatic spasmolytic polypeptide (PSP): II. Radioimmunological determination of PSP in porcine tissues, plasma and pancreatic juice.

A radioimmunoassay (RIA) for the determination of porcine Pancreatic Spasmolytic Polypeptide (PSP) has been developed. The antisera raised in rabbits were sensitive to 5 pgequiv. of PSP in a volume of 100 microliter. Immunoreactive PSP (IR-PSP) has been determined in extracts from 22 porcine organs. Pancreas was found to be the only organ containing substantial amounts of IR-PSP (0.1 mgequiv. IR-PSP/g wet weight). The fasting porcine plasma level of IR-PSP was about 10 ngequiv./ml, corresponding to 850 pM. The concentration of IR-PSP in porcine pancreatic juice varied from 0.2 mugequiv./ml in the fasting state to 46-116 mugequiv./ml after stimulation with pancreozymin or secretin. A linear correlation was found between the exocrine secretion of IR-PSP and total protein.

Animals↗

PubMed1986

Receptor binding of pancreatic spasmolytic polypeptide (PSP) in rat intestinal mucosal cell membranes inhibits the adenylate cyclase activity.

The recently isolated pancreatic spasmolytic polypeptide, PSP, interacted with specific binding sites in the gastrointestinal tract and inhibited the adenylate cyclase activity in rat intestinal mucosal cell membranes. The binding sites appeared to be heterogeneous and Scatchard analysis of the binding data indicated the presence of at least two classes of sites. The high-affinity low-capacity binding sites and the low-affinity high-capacity binding sites had apparent dissociation constants of 1.3 X 10(-7) mol/l and 4.2 X 10(-6) mol/l, respectively. The PSP induced inhibition of the adenylate cyclase activity was independent of the stimulatory state of the enzyme. The basal activity as well as that stimulated by VIP and secretin was half maximally inhibited at approximately 3 X 10(-5) mol/l of PSP. The inhibitory effect of PSP was independent of the agonist concentration employed. PSP did not affect the receptor binding of VIP nor did VIP affect the receptor binding of PSP.

Adenylyl Cyclase Inhibitors↗

PubMed1988

Receptor binding of pancreatic spasmolytic polypeptide in intestinal mucosal cells and membranes.

Rat intestinal mucosal cells contain receptors for pancreatic spasmolytic polypeptide (PSP). The binding of 125I-PSP was rapid, saturable, reversible and specific. PSP competed with 125I-PSP for binding to the receptors and 10(-7) M of PSP half-maximally inhibited 125I-PSP binding. The normalized PSP dose-response graphs in intact cells and crude membranes were superimposable. Scatchard plots of PSP binding to membranes were curvilinear, indicating multiple classes of binding sites, negative cooperative interaction between sites or a combination of both. PSP increased the rate of dissociation of the 125I-PSP-receptor complex compared to the rate observed by dilution only, thus giving evidence that negative cooperative interaction may occur between PSP binding sites. The half-life of the fast dissociating complex was about 1.5 min and that of the slow dissociating complex 38 min. These values were independent of the receptor occupancy. The increased rate of dissociation at high receptor occupancy stemmed from a shift in the ratio of the pool sizes of fast and slow dissociating receptor complexes.

Animals↗