scholarly journals Effect of 1-acyl-5,6-dimethoxy / diethoxy-2-methylthiobenzimidazoles on APD90 and isometric contraction in guinea pig atrium and aortic preparations activated by carbachol and phenylephrine

2010 ◽  
Vol 17 (3-4) ◽  
pp. 77-82
Author(s):  
Vida GARALIENĖ ◽  
Linas LABANAUSKAS ◽  
Algirdas BRŪKŠTUS ◽  
Vygantas BARSYS
Keyword(s):  
Blood Vessel ◽  
Guinea Pig ◽  
Isometric Contraction ◽  
Force Transducer ◽  
Benzimidazole Derivatives ◽  
Contraction Force ◽  
Phenylephrine Hydrochloride ◽  
Dose Dependent Fashion ◽  
Guinea Pig Atrium ◽  
Dose Dependent

Studies have shown that 1-acyl-5,6-diethoxy-2-methylthiobenzimidazole derivatives 3-pyridyl-(1); 2-pyridyl- (2); 4-thiazolyl- (3); 4-pyridyl- (4); methyl- (5); 2-thienyl- (6) and 1-acetyl-5,6-dimethoxy-2-methylthiobenzimidazole (7) exhibit positive inotropic properties. The goal of the study was to investigate the effects of the above-mentioned compounds in restoring a decreased isometric contraction and APD90 induced by carbachol in an isolated guinea pig atrium, and to relax the aortic rings precontracted by phenylephrine. Isometric contraction and APD90 were recorded by using a force transducer and standard microelectrode technique (stimulation rate 1 Hz). Carbachol (1 μM) caused a decrease of the isometric contraction and APD90 on an overage by 63.2% and 49.6%, respectively. Compounds 1–5 used in a dose-dependent fashion (10–500 μM) abolished the action of carbachol and restored the contraction force and APD90 in the electrically driven atrium significantly; compound 2 reversed the APD90 to the baseline. Compounds 2 and 7 antagonized the contraction of aortic rings evoked by phenylephrine (10–4 M) and caused their relaxation by 24.4% and 17% at a dose of 10–4 M and by 76.2% and 72.5% at a dose of 5 × 10–4 M in groups 2 and 7, respectively. Conclusion. The results presented in the study have shown that some 1-acyl-5,6-dimethoxy / diethoxy-2-methylthiobenzimidazoles are able to abolish the effects of carbachol and phenylephrine on the AP duration and isometric contraction in guinea pig atrium and blood vessels. These data will contribute to the synthesis of targeted compounds with positive inotropic and blood-vessel relaxing characteristics among benzimidazole derivatives, which could be useful in clinical practice. Keywords: 1-acyl-2-methylthio-5,6-dimethoxy / diethoxybenzimidazoles, guinea pig atrium, blood vessel, phenylephrine hydrochloride, carbamylcholine chloride

Growth hormone secretion in the guinea-pig

1990 ◽  
Vol 124 (3) ◽  
pp. 371-380 ◽  
Author(s):  
B. Gabrielsson ◽  
K. M. Fairhall ◽  
I. C. A. F. Robinson
Keyword(s):  
Growth Hormone ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Physiological Control ◽  
Gh Secretion ◽  
Dose Dependent Fashion ◽  
Growth Promoting ◽  
Dose Dependent

ABSTRACT The guinea-pig is unusual in that it continues to grow at a normal rate after hypophysectomy. Although its pituitary gland appears to contain a GH, this has not been isolated or characterized, and nothing is known about its secretion or physiological control. We have identified guinea-pig GH, established a sensitive heterologous radioimmunoassay and adapted our automatic blood microsampling method to study spontaneous GH secretion in this species. In male guinea-pigs, GH is released in an episodic pattern, reminiscent of the rat. Large multicomponent pulses of GH secretion occur every 3–4 h between periods of low or undetectable GH release, whereas most females showed a more uniform pulsatile pattern with pulses every 1–2 h. GH was released in response to GH-releasing factor (GRF) injections (2, 10 or 20 μg [Nle27]-GRF(1–29)NH2) in a dose-dependent fashion, and i.v. infusion of somatostatin (50 μg/h) blocked spontaneous GH pulses, eliciting a rebound release (from 2·0±0·8 (s.e.m.) to 36±17 μg/l 30 min after stopping the infusion). Infusions of a GH-releasing hexapeptide (100 or 400 μg/h for 4 h) also released GH. These results provide the first description of the pattern of GH release in the guinea-pig, and suggest that the striking episodic pattern is controlled by the same hypothalamic peptides that regulate GH in other species. Since the guinea-pig grows well in the absence of GH, this species may use GH for its metabolic, rather than growth-promoting actions. The guinea-pig may well prove a useful model, now that methods are available for studying its endogenous GH secretion. Journal of Endocrinology (1990) 124, 371–380

Effects of Platelet-Activating Factor on Leukocyte Adhesion in the Guinea Pig Aorta

1985 ◽  
Vol 43 ◽  
pp. 684-685
Author(s):  
Mary Kay Melden ◽  
Ronald G. Van Valen ◽  
Robert N. Saunders ◽  
Dean A. Handley
Keyword(s):  
Blood Vessel ◽  
Guinea Pig ◽  
Intravenous Injection ◽  
Leukocyte Adhesion ◽  
Platelet Activating Factor ◽  
Dependent Manner ◽  
Cardiac Effects ◽  
Small Vessels ◽  
Dose Dependent

Platelet-activating factor (PAF) is a potent mediator of immune anaphylaxis. In a dose-dependent manner, PAF can induce such effects as thrombocytopenia, neutropenia, hypotension, bronchoconstriction, hemoconcentration, and negative inotropic cardiac effects. By intradermal or intravenous injection, PAF has been shown to induce blood vessel hyperpermeability resulting in extravasation of plasma, leukocyte adhesion and subsequent diapedesis. However, most studies of endothelial-leukocyte interactions have been limited to small vessels. We have examined the effects of PAF on endothelial structure and leukocyte involvement in the guinea pig aorta.

Antagonism by theophylline of the adenosine receptor agonist 5′-N-ethykarboxamidoadenosine at the guinea pig ileum

1985 ◽  
Vol 63 (9) ◽  
pp. 1195-1197 ◽  
Author(s):  
F. L. Christofi ◽  
M. A. Cook
Keyword(s):  
Guinea Pig ◽  
Receptor Agonist ◽  
Acetylcholine Release ◽  
Receptor Site ◽  
Inhibitory Effect ◽  
Guinea Pig Ileum ◽  
Competitive Antagonism ◽  
Adenosine Receptor Agonist ◽  
Dose Dependent Fashion ◽  
Dose Dependent

The inhibitory effect of the putative adenosine A2 receptor agonist 5′-N-ethylcarboxamidoadenosine (NECA) on acetylcholine release from the stimulated guinea pig ileum preparation and the nature of its antagonism by theophylline were investigated. NECA was shown to inhibit the response of the ileum preparation in a dose-dependent fashion, and an EC50 value of 1.62 × 10−8 M was determined. This value was comparable with that determined for the A1 receptor agonist N6-R-phenylisopropyladenosine (R-PIA) (2.57 × 10−8 M) using the same preparation. Competitive antagonism of the inhibitory effect of NECA by theophylline was quantitated and a pA2 value of 5.04 for the methylxanthine was obtained. This value was similar to those obtained previously for R-PIA and adenosine itself and suggests that these nucleosides may be interacting with the same receptor site on myenteric nerve endings. These findings do not permit the designation of the receptor as an A1 or A2 subtype according to current criteria.

Effects of roxithromycin and erythromycin on interleukin 8-induced neutrophil recruitment and goblet cell secretion in guinea pig tracheas.

1996 ◽  
Vol 40 (7) ◽  
pp. 1726-1728 ◽  
Author(s):  
J Tamaoki ◽  
J Nakata ◽  
E Tagaya ◽  
K Konno
Keyword(s):  
Guinea Pig ◽  
Goblet Cell ◽  
Neutrophil Recruitment ◽  
Interleukin 8 ◽  
Cell Secretion ◽  
A Value ◽  
Dose Dependent Fashion ◽  
Dose Dependent

Inhaled interleukin 8 caused an increase in goblet cell secretion in guinea pig tracheas, which was accompanied by mucosal infiltration of neutrophils. These responses were inhibited by pretreatment with roxithromycin or erythromycin in a dose-dependent fashion. Macrolides may thus be a value in protecting against neutrophil-associated airway hypersecretion.

Rheumatoid Factor in the Serum of Hepatitis C Virus-Infected Patients: An Increase in the Titre during Cold Storage

1996 ◽  
Vol 33 (5) ◽  
pp. 438-442 ◽  
Author(s):  
Kazuhito Ueda ◽  
Toshimasa Nakagawa ◽  
Akira Shimizu ◽  
Hideto Nakajima ◽  
Akira Fukuda ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Guinea Pig ◽  
Rheumatoid Factor ◽  
Cold Storage ◽  
Complement Components ◽  
Fresh Serum ◽  
Dose Dependent Fashion ◽  
Dose Dependent ◽  
Pig Serum

Storage of serum at 4°C elevated the titre of rheumatoid factor (RF) as measured by nephelometry with IgG-coated latex in 12 of 38 specimens positive for hepatitis C virus. Increased RF following cold storage was not detected in HCV-negative sera. Most of the sera showing the cold-dependent elevation of RF had decreased complement hemolytic activity (CH50) after the cold storage. The RF titre elevated by cold storage decreased to the level of fresh serum by the addition of guinea pig serum as a complement supplement in a dose-dependent fashion. Thus, in the serum of some HCV-infected patients, the affinity of RF appears to be weak, and the binding between the RF and IgG coated on latex may be inhibited by the complement components of fresh serum.

scholarly journals Anticholinergic effect of 2-aminopyridine and its sulfonylcarbamide derivatives on electromechanical activity in guinea pig atrium

Medicina ◽  
2007 ◽  
Vol 43 (10) ◽  
pp. 808 ◽  
Author(s):  
Vida Gendvilienė ◽  
Danguolė Zablockaitė ◽  
Irma Martišienė ◽  
Herta Gurskaitė ◽  
Antanas Stankevičius
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Action Potential Duration ◽  
Pyridine Ring ◽  
Muscarinic Acetylcholine Receptor ◽  
New Drugs ◽  
Anticholinergic Effect ◽  
Contraction Force ◽  
Control Modification ◽  
Guinea Pig Atrium

The aim of the study was to investigate an action of 2-aminopyridine and its new sulfonylcarbamide derivatives 2-AP21, 2-AP22, 2-AP26, and 2-AP27 (10–5–10–3 M) on carbachol-induced shortening of action potential duration and reduction of contraction force in guinea pig atrial muscles. Experiments were carried out using a standard method of myocardium electromechanical activity registration. Under control conditions (perfusion of atrial strips with Tyrode solution), an average of action potential duration, measured at 90% (AP90) and 50% (AP50) of repolarization, were 112.32±6.07 ms and 50.21±3.25 ms, (n=19), respectively, and contraction force was of 1.42±0.28 mN (n=20). Carbachol (10–6M), an agonist of muscarinic acetylcholine receptor and activator of KAch channels, markedly decreased AP90 to 35.31±4.21%, AP50 – to 26.42±2.66% (n=19) (P<0.001), and contraction force – to 24.23±2.0% (n=20) (P<0.001) vs. control. Modification of 2-aminopyridine structure by replacing 2-amino group by 4-toluolsulfonylcarbamide fragment and quaternization of nitrogen in pyridine ring increased anticholinergic effect on action potential duration and contraction force. According to their maximal prolongation of AP at 90% of repolarization, all new drugs ranked as follows: 2-AP27>>2-AP26>2-AP22³2-AP>2-AP21. 2-aminopyridine derivative 2-AP27, containing 4-toluolsulfonylcarbamide fragment and 4-nitrobenzyl radical at quaternized nitrogen of the pyridine, had the most potent anticholinergic effect on AP90 (936.60±178.23%). 2-AP22 and 2-AP26 (containing methyl or allyl radicals at quaternized nitrogen of the pyridine, respectively) showed a much weaker anticholinergic effect (231.39±28.48% and 318.25±63.81%, respectively). The weakest anticholinergic effect (63.59±34.38%) was induced by 2-aminopyridine derivative 2-AP21, which had non-quaternized nitrogen of the pyridine.

Plasminogen Interactions with Immobilized Fibrinogen

1989 ◽  
Vol 62 (04) ◽  
pp. 1078-1082 ◽  
Author(s):  
Burt Adelman ◽  
Patricia Ouynn
Keyword(s):  
Immunosorbent Assay ◽  
Aminocaproic Acid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Binding Regions ◽  
Dose Dependent Fashion ◽  
Epsilon Aminocaproic Acid ◽  
Dose Dependent

SummaryThis report describes the binding of plasminogen to fibrinogen adsorbed onto polystyrene wells. Binding was determined by enzyme linked immunosorbent assay. Both glu- and lys-plasminogen bound to immobilized fibrinogen in a dose-dependent fashion. However, more lys- than glu-plasminogen bound when equal concentrations of either were added to immobilized fibrinogen. Plasminogen binding was inhibited by epsilon aminocaproic acid indicating that binding was mediated via lysine-binding regions of plasminogen. Soluble fibrinogen added in excess of immobilized fibrinogen did not compete for plasminogen binding but fibrinogen fragments produced by plasmin digestion of fibrinogen did. Treatment of immobilized fibrinogen with thrombin caused a small but significant (p <0.01) increase in plasminogen binding. These studies demonstrate that immobilized fibrinogen binds both glu- and lys-plasminogen and that binding is mediated via lysine-binding regions. These interactions may facilitate plasminogen binding to fibrinogen adsorbed on to surfaces and to cells such as platelets which bind fibrinogen.

Soluble Thrombomodulin Purified from Human Urine Exhibits a Potent Anticoagulant Effect In Vitro and In Vivo

1995 ◽  
Vol 73 (05) ◽  
pp. 805-811 ◽  
Author(s):  
Yasuo Takahashi ◽  
Yoshitaka Hosaka ◽  
Hiromi Niina ◽  
Katsuaki Nagasawa ◽  
Masaaki Naotsuka ◽  
...  
Keyword(s):  
Human Urine ◽  
Specific Activity ◽  
Anticoagulant Activity ◽  
Rabbit Lung ◽  
Soluble Thrombomodulin ◽  
Molecular Weights ◽  
Dose Dependent Fashion ◽  
Dose Dependent

SummaryWe examined the anticoagulant activity of two major molecules of soluble thrombomodulin purified from human urine. The apparent molecular weights of these urinary thrombomodulins (UTMs) were 72,000 and 79,000, respectively. Both UTMs showed more potent cofactor activity for protein C activation [specific activity >5,000 thrombomodulin units (TMU)/mg] than human placental thrombomodulin (2,180 TMU/mg) and rabbit lung thrombomodulin (1,980 TMU/mg). The UTMs prolonged thrombin-induced fibrinogen clotting time (>1 TMU/ml), APTT (>5 TMU/ml), TT (>5 TMU/ml) and PT (>40 TMU/ml) in a dose-dependent fashion. These effects appeared in the concentration range of soluble thrombomodulins present in human plasma and urine. In the rat DIC model induced by thromboplastin, administration of UTMs by infusion (300-3,000 TMU/kg) restored the hematological abnormalities derived from DIC in a dose-dependent fashion. These results demonstrate that UTMs exhibit potent anticoagulant and antithrombotic activities, and could play a physiologically important role in microcirculation.

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