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Biomedical subjects

V Petkov

Publications and source records attributed to V Petkov.

At least 73 records · Page 4Linked to original sources
PubMed1979

Pharmacological studies of a group of semi-synthetic structural analogues of glaucine.

Glaucine and the newly-synthesized compounds possess some general properties conditioned by the common apomorphine structure - inhibition of the central nervous system, brief decrease in blood pressure and spasmolytic action. At the same time the changes in the structure of glaucine lead to quantitative or qualitative changes in some of its effects. Substitution of hydrogen in 3rd position with -CH2. NH-group reduces glaucine toxicity 3.5 times. Still greater decrease in the toxicity (7.5-10 times) is found in the case of N-oxidation or dehydrogenation of glaucine. The extension of the methyl group in 3rd position with a hydroxy group or with an amide residue of the benzoic acid, as well as the dehydrogenation and N-oxidation of glaucine, lead to intensification of the inhibitory action on the central nervous system. With the exception of 7-methyl dehydroglaucine which has antitussive action similar to glaucine, the other glaucine structural analogues do not possess this property. Both glaucine and its structural analogues exercise a bronchoconstrictor effect. 3-Aminomethyl derivatives preserve the spasmolytic activity of glaucine, and their several-fold lower toxicity makes them more promising spasmolytic agents than glaucine. Dehydrogenation and N-oxidation of glaucine reduce considerably its spasmolytic action.

Alkaloids↗
PubMed1978

The character of the antagonism by polyphloretin phosphate of contractions to prostaglandins E1 and F 2alpha in guinea-pig ileum.

Polyphloretin phosphate (PPP) produced a dose-dependent decrease in the tone and reduction of the spontaneous phasic contactions of the longitudinal muscle of guinea-pig isolated ileum. PPP (100 microgram ml-1) after a 2 min contact with the ileum decreased the contractile effects of PGE1 0.1 micron by 40.6 +/- 7.4%, of PGE1 0.01 micron by 86.7 +/- 3.3% and of PGE2alpha 0.1 micron by 62.2 +/- 8.6%. After 10 min contact of PPP the contractile effect of PGE1 0.1 micron was decreased by 47.7 +/- 4.7% and that of PGE2alpha 0.1 micron by 89.6 +/- 1.7%. When the contact was longer, PPP showed a pronounced after-effect in respect to the effects of PGE1 and particularly of PGF2alpha. PPP signicantly reduced contractions to 5-HT and BaCL2, but not to acetylcholine, histamine or substance P. The type of antagonism of PGE1 by PPP was examined using cumulative concentration-effect curves for PGE1 in the presence of increasing concentrations of PPP. We conclude that on guinea-pig ileum PPP acts as a non-competitive antagonist of PGE1 and PGF2alpha.

Acetylcholine↗
PubMed1978

[Effect of ionizing radiation on cerebral phosphodiesterase].

The authors examined the influence of x-ray irradiation on phosphodiesterase system in the brain of rats and the sensitivity of the enzyme to inhibitors (caffeine, theophyline, thyopental) and activators (imidozol). The animals (Wistar with weights of 150--200 gm/were irradiated singly with a dose of 737 r. Phosphodiesterase activity (PD) was determined by the method of Filburn and Carn (1972) at two substrate concentrations (1 and 100 microM). X-ray irradiation did not change PD with high Km, while the enzyme with low Km was reduced significantly and transitionaly. Caffeine, theophyline and thyopental inhibited more PD with low Km in the irradiated rats in comparison with the control nonirradiated rats. The activating effect of imidazol on PD with low Km was more marked in irradiated rats. These data could be interpreted in the light of the molecular mechanisms, determining the altered action of some drugs after x-ray irradiation.

Animals↗
PubMed1978

Comparative studies of colon reactivity of healthy and ionization-radiated guinea-pigs to some spasmogens and their antagonists.

Comparative studies were carried out of the contractile effects of acetylcholine (1 X 10(-6) M), histamine (1 X 10(-6) M), serotonin (1 X 10(-5) M), nicotine (1 X 10(-5) M), BaCl2 (1 X 10(-3) M) and of the influence on the induced contractions caused by the antagonists of these spasmogens, namely: atropin (1 X 10(-6) M), dipenhydramine (1 X 10(-6) M), benzyloxygramine (1 X 10(-5) M), hexamethonium (1 X 10(-5) M) and papaverine (1 x 10(-5) M) on isolated segment of guinea-pig colon. Experimental acute radiation sickness is found to induce considerable changes in the reactivity of the intestinal smooth-muscle preparation used to the spasmogens applied and to their antagonists. Depending on the nature of the pharmacological agents, the degree of development of the experimental acute radiation sickness, and on other factors, the changes in the reactivity to the drugs tested revealed very great qualitative and quantitative differences. The following more definite changes could be pointed out. The spastic effects of serotonin and BaCl2 were potentiated, while the spastic effects of histamine and nicotine showed a tendency toward decrease. Under conditions of acute radiation sickness tha antagonistic effect of atropine to acetylcholine was intensified, while the antagonistic effects of benzyloxygramine to serotonin, of hexamethonium to nicotine and of papaverine to BaCl2, grew weaker. Diphenhydramine showed potentiated antagonistic effect to histamine on the 72nd h after radiation. Certain possibilities are discussed concerning the mechanisms underlying the changes in the reactivity of the intestinal smooth muscle to pharmacological agents, induced by acute radiation sickness.

Acetylcholine↗
PubMed1978

Role of calcium in the mechanism of action of the prostaglandins E1 and F2 alpha as well as of their antagonist polyphloretin phosphate (PPP).

The contractile effect of PGE1 on guinea-pig ileum is not changed either by increase (to 4 mM) or by decrease (to 1 mM) of the Ca++ content in Krebs solution. The decrease of Ca++ in the medium intensifies the contractile effect of PGE2 alpha. Reduction of Ca++ weakens the antagonistic effect of PPP (100 micrograms/ml) against PGF2 alpha. PPP has a marked aftereffect with respect to the effects of PGF2 alpha--in cases of normal Ca++ content in the Krebs solution this aftereffect appears upon longer (10 min) contact of PPP with the intestinal segment, while in cases of changed Ca++ content it appears already after 2-min PPP action. It is concluded that in order to induce contractions in the guinea-pig ileum, PGE1 and PGF2 alpha utilize the internal Ca++. It is assumed that PGF2 alpha increases the reactivity of the anionic sites of the smooth-muscle membrane for Ca++. As a result of this, the complex compounds of Ca++ at its higher concentration make more difficult the realization of the contractile process. It is assumed that Ca++ is needed for the maximum manifestation of the antagonistic effect of PPP.

Animals↗
PubMed1977

Studies on the phosphodiesterase in various organs of rats and guinea-pigs of different ages and different sex.

The method of Butcher and Sutherland is used to determine the phosphodiesterase activity of various organ homogenates from rats and guinea-pigs of different age and sex. The different rat organs manifest great differences in their phosphodiesterase activity. Especially high phosphodiesterase activity is found in the adrenal gland and in the brain cortex. Sex is not found to be related to definite differences in the activity of the enzyme. In some organs age differences are established both in the phosphodiesterase activity and in the degree of its inhibition or activation by inhibitors and stimulators of the enzyme. It is assumed that in some organs age conditions changes not only in the general phosphodiesterase activity, but also in the ratio between its isoenzymes.

Age Factors↗
PubMed1977

Influence of indomethacin and aspirin on the contractile effects of prostaglandin F2alpha (PGF2alpha) at different Ca++ concentrations (experiments on guinea-pig ileum).

The direct effect of the prostaglandine synthetase inhibitors indomethacin and aspirin on the contractile effects of PGF2alpha at different Ca++ concentrations (1.5, 2.5 and 3.5 mM) in the Krebs solution was studied on isolated segments of guinea-pig ileum. It is established that after contact with indomethacin (3 X 10(-5) M) for 1-5 min the contractile effect of PGF2alpha (1 X 10(-7) M) decreases by 20-60%. Higher Ca++ content in the Krebs solution weakens the direct inhibitory effect of indomethacin. Unlike indomethacin, aspirin has no significant direct effect on prostaglandine contractions. Increase of Ca++ in the Krebs solution by 1 mM in itself does not change significantly the effect of PGF2alpha. Having in mind analogous results obtained in previous experiments with PGE1, it is concluded that indomethacin but not aspirin exercises a direct antagonistic action to the contractile effects of PGF2alpha and PGE1 on the guinea-pig ileum. The degree of this antagonistic action is in a definite dependence on the concentration of extracellular Ca++. Discussing the possible mechanisms of direct inhibitory action of indomethacin on the PGE1 and PGF2alpha effects on guinea-pig ileum, assumptions are made concerning the effect of indomethacin on the utilization of external Ca++ and the noncompetitive antagonistic action of indomethacin as a result of the interaction with allosteric (allotopic) sites of the prostaglandine receptor system.

Animals↗
PubMed1977

Nicotine-like effect of prostaglandin F2alpha on longitudinal smooth muscle of cat jejunum.

The effect of hexamethonium (1 x 10(-6) M) chlorpromazine (1 x 10(-6) M) and physostigmine (1 x 10(-7) M) on the spastic effects of PGF2alpha (3 x 10(-7) M), PGE1 (3 x 10(-7) M) acetylcholine (1 x 10(-8) M) and nicotine (1 x 10(-7) M), was studied on isolated longitudinal smooth muscle of cat jejunum. The contractile effects of PGF2alpha and nicotine were found to decrease on an analogous scale as a result of hexamethonium and chlorpromasine administration and to be potentiated by physostigmine. Hexamethonium and chorpromazine do not influence significantly the spastic effects of acetylcholine, physostigmine potentiates them less markedly. Hexamethonium reduces whereas physostigmine and chlorpromazine potentiate the contractile effect of PGE1. Taking into consideration also the results of previous studies (Petkov, Radomirov, 1977), it is assumed that the contractile effect of PGF2chi on the longitudinal muscle of cat jejunum is at least partly mediated through ganglionic stimulation, i.e. the mechanism of the spastic action of PGF2chi on the smooth muscle used has at least partly a nicotine-like character.

Animals↗
PubMed1976

Participation of adrenergic mechanisms in the genesis of the cortical brain electrical activity.

The changes both in the spontaneous and in the evoked electrical activity of the somatosensory cortex, occurring after local or systematic administration of chlorpromazine, have been studied on 36 cats. The neuroleptic used weakens both the spontaneous cortical electrical activity and that induced by stimulation of n. radialis and of MRF. The potentials evoked by stimulation of VPL do not change. Systematic administration of chlorpromazine causes analogous changes in the electrical activity of the somatosensory cortex. Stimulation of n. radialis and MRF, though not of VPL, results in a sharp increase in the activity of the adenylate cyclase in the somatosensory cortex. Local administration of chlorpromazine leads to statistically significant less marked increase in response to applied stimulations of the adenylate cyclase activity. The results obtained substantiate the assumption that adrenergic neurones participate in the formation both of the spontaneous and of the induced electrical activity in the somatosensory cortex of cats.

Adenylyl Cyclases↗
PubMed1976

[Role of calcium ions in the contractile effects of acetylcholine (experiments on the guinea pig vas deferens)].

The authors carried out experiments on isolated vasa deferentia, obtained from a guinea pig. Recordings of the isotonic contractile activity was made by means of a strain gauge. Ink records were made on graduated tape of miliampermeter Tesla. Acethylcholine was used in a concentration of 1 X 10(-5) M, but serotonine-in a concentration of 1 X 10(-5) M. Growing reduction of the values was observed very regularly in all experiments both in the serotonine and acethylcholine contractions of vas deferens after diminution of the content of calcium in the Krebs solution from 0,9 to 0,15 mM. Gradual recovery of the value of the spastic effects of the examined substances was observed after placing the isolated organ in Krebs solution with a normal content of calcium. In analogous role of calcium in the spastic effects of the two mediators there were also some differences in the dynamics on which this role was manifested. The authors discussed the significance of the external calcium for the realization of the contractile effects of acethylcholine and serotonine on vas deferens of a guinea pig.

Acetylcholine↗
PubMed1976

[Changes in the concentration of biogenic monoamines in different brain regions under the influence of centrophenoxine (experiments on rats)].

The authors administered 50 mg/body weight of centrophenoxine in white rats i.p. for five susseccive days. The content of serotonine in the cerebral cortex, brain stem and cerebellum increased statistically significant in the rats, injected with centrophenoxine. The levels of noradrenaline and dopamine in the brain stem were raised also significantly. Centrophenoxine did not alter the content of cyclic AMP and the activity of phosphodiesterase in the cerebral cortex and brain stem. These data gave foundation to the authors to suggest that in the mechanism of action of centrophenoxine a significant role is given to the changes, induced by this preparation in the content of biogenic amines in the brain stem.

Animals↗
PubMed1975

Differential inhibition of phosphodiesterase according to the organ origin of the enzyme.

Essential differences in the degree of papaverine [5 x 10(-5) M]- and theophylline [1 x 10(-3) M]-induced inhibition of cyclic nucleotide phosphodiesterase (PDE) were found in homogenates from different structures of the CNS as well as from different organs of male albino rats. Both inhibitors of PDE showed a mosaic pattern of their inhibitory effects on the enzyme activity of the brain structures tested. Papaverine inhibited PDE by 36 percent in the spinal cord, 53 percent in the cerebellum, 56 percent in the cortex, and 75 percent in the brain stem. Theophylline inhibited PDE least in the cerebellum (26 percent ) and most markedly in the brain stem (68 percent). Still larger differences were observed in the inhibitory action of papaverine and theophylline on PDE of the organs tested (e.g., papaverine inhibited PDE by 6 percent in the heart and 73 percent in the spleen; theophylline inhibited PDE by 26 percent in the adrenals and by 72 percent in the heart. The mosaic sensitivity of PDE in different organs and brain structures to papaverine and theophylline was considered as an expression of isoenzyme heterogeneity.

Animals↗