The influence of carbamate local anesthetics on the occurrence of experimental gastric ulcers.

Evaluation of the antiulcer effects of a series of 2-piperidineethylesters of o-alkoxy-substituted phenylcarbamic acids were performed using two experimental models of gastric ulcers, e.g. induced by stress or by ligation of the pylor. It was found that these models were not identical. In the case of stress-induced ulcers, no experimental animal died as compared to the second experimental group with a 30% mortality rate due to the more frequent occurrence of ulcer perforations. Result similarities of both models could only be found with respect to the range of damage of the mucous membrane of the stomach. A premedication of rat with basic carbamates in the dose 20 mg.kg-1 p.o. resulted in a reduced incidence of stress- and ethanol-induced ulcerous lesions. The most significant antiulcer activity was found using compounds designated as the No. XIII, XVI and XIX. Pretreatment of rats with basic carbamates in the case of Shay ulcers has again resulted in a reduced range of ulcer lesions which was most expressive using compounds No. XVI and XIX.

[Radioprotective effects of basic copper carboxylate complexes]. / Radioprotektivní úcinek nekterých základních karboxylatomednatých komplexu.

The radioprotective activity of eight selected copper (II) carboxylates--Cu (RCOO)2.nL (R = alkyl, aryl, 2-furyl and 2-thienyl; L usually represents water)--was assayed in a model of lethally gamma-irradiated (9 Gy, 0.97 Gy/min) mice. The compounds tested were applied (as solutions in saline) s.c. in three single doses of 20 mumol/kg 48.24 and 6 h before irradiation. The highest radioprotective effects were measured by survival of mice achieved after premedication of animals with copper (II) 2-thenoate monohydrate (77%), copper (II) acetylsalicylate (64%), copper (II) 2-methoxybenzoate monohydrate (62%) and copper (II) acetate monohydrate (54%). On the other hand, survival of vehicle-pretreated mice was only 10%. The observed biological properties of complexes are discussed in relation to their structures.

[Anti-ulcer effectiveness of mono- and dibasic carbamates with local anesthetic effects]. / Studium antiulcerózního úcinku mono a dibazických karbamátu s lokálne anestetickou úcinností.

An evaluation of anti-ulcer effects of mono- and dibasic carbamate local anaesthetics was performed using two experimental models of gastric ulcers, i.e. those induced by stress, or by ligation of the pylorus. These models have been found not to be identical. In the case of stress-induced ulcers, no experimental animal died as compared to the second experimental group with a 30% mortality rate due to the more frequent occurrence of ulcer perforations. Result similarities of both models could only be found with respect to the range of damage of the mucous membrane of the stomach. A premedication with a majority of basic carbamates decreased the incidence and range of ulcer lesion. The anti-ulcer activity of monobasic carbamates was more significant when compared with dibasic compounds.

Contractility and inhibition of protein phosphatases by cantharidin.

1. Cantharidin is a natural defensive toxicant produced by blister beetles. 2. Cantharidin shares structural similarity with highly toxic commercial herbicides (e.g., endothall, endothall anhydride and endothall thioanhydride). 3. Cantharidin inhibits the activity of purified catalytic subunits of serine/threonine protein phosphatases (PP) type 1 and type 2A. 4. Cantharidin increases force of contraction in isolated myocardial and vascular preparations. 5. Cantharidin enhances the phosphorylation state of myocardial and vascular regulatory proteins. 6. Cantharidin is a valuable tool for studying the function of PP in regulatory phosphorylation-dephosphorylation events.

Postnatal changes in contractile time parameters, calcium regulatory proteins, and phosphatases.

Compared with isolated electrically driven neonatal ventricular preparations, the total time of contraction, the time to peak tension, and the time of relaxation were decreased to approximately 50% in adult ventricular preparations. The expression of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) was increased to 133% at the protein level and to 154% at the mRNA level in adult vs. neonatal ventricular preparations, whereas phospholamban was unchanged at both the protein and mRNA levels. Moreover, Ca2+ uptake was increased to 180% in adult vs. neonatal ventricular preparations. Phospholamban phosphorylation was enhanced in adult vs. neonatal ventricular preparations. In adult ventricular preparations, phosphatase activity was reduced to 53% of neonatal preparations, the protein levels of the immunologically detectable catalytic subunits of protein phosphatase types 1 and 2A were reduced to 28 and 61% of neonatal preparations, respectively, and the mRNA levels of type 1alpha, 1beta, 1gamma, 2Aalpha, and 2Abeta phosphatase isoforms were decreased to 69, 68, 54, 67, and 63%, respectively. We conclude that in the adult rat heart, the shortened time parameters of contraction can be explained by an elevated expression of SERCA. In addition, an increased phosphorylation state of phospholamban due to reduced phosphatase activity may be involved.

Inotropic effects of diadenosine tetraphosphate (AP4A) in human and animal cardiac preparations.

Diadenosine tetraphosphate (AP4A) is an endogenous compound and exerts diverse physiological effects in animal systems. However, the effects of AP4A on inotropy in ventricular cardiac preparations have not yet been studied. The effects of AP4A on force of contraction (FOC) were studied in isolated electrically driven guinea pig and human cardiac preparations. Furthermore, the effects of AP4A on L-type calcium current and [Ca]i were studied in isolated guinea pig ventricular myocytes. In guinea pig left atria, AP4A (0.1-100 microM) reduced FOC maximally by 36.5 +/- 4.3%. In guinea pig papillary muscles, AP4A (100 microM) alone was ineffective, but reduced isoproterenol-stimulated FOC maximally by 29.3 +/- 3.4%. The negative inotropic effects of AP4A in atria and papillary muscles were abolished by the A1-adenosine receptor antagonist 1, 3-dipropyl-cyclopentylxanthine. In guinea pig ventricular myocytes, AP4A (100 microM) attenuated isoproterenol-stimulated L-type calcium current and [Ca]i. In human atrial and ventricular preparations, AP4A (100 microM) alone increased FOC to 158.3 +/- 12.4% and 167.5 +/- 25.1%, respectively. These positive inotropic effects were abolished by the P2-purinoceptor antagonist suramin. On the other hand, AP4A (100 microM) reduced FOC by 27.2 +/- 7.4% in isoproterenol-stimulated human ventricular trabeculae. The latter effect was abolished by 1,3-dipropyl-cyclopentylxanthine. In summary, after beta adrenergic stimulation AP4A exerts negative inotropic effects in animal and human ventricular preparations via stimulation of A1-adenosine receptors. In contrast, AP4A alone can exert positive inotropic effects via P2-purinoceptors in human ventricular myocardium. Thus, P2-purinoceptor stimulation might be a new positive inotropic principle in the human myocardium.

Inotropic effects of diadenosine tetraphosphate in isolated canine cardiac preparations.

We studied the effects of diadenosine tetraphosphate (AP4A) on the force of contraction in canine preparations. The force of contraction was measured in isolated electrically driven (1 Hz) atrial and ventricular cardiac trabeculae from adult dogs. AP4A (100 microM) alone and after prestimulation with 10 nM isoproterenol reduced force of contraction in atrial preparations by approximately 24%. Moreover, AP4A (100 microM) alone and after prestimulation with 10 nM isoproterenol reduced the force of contraction in ventricular preparations by 29 and 29%, respectively. The negative inotropic effects of AP4A were abolished by the A1-adenosine receptor antagonist 1,3-dipropyl-cyclopentyl-xanthine (DPCPX). In summary, in canine myocardium, AP4A alone and after prestimulation with a beta-adrenoceptor agonist exerts negative inotropic effects, which are probably mediated via A1-adenosine receptors.