Role of the GABA-ergic link in the development of the tranquilizing effect in cats

The development of the tranquilizing effect of n-dipropylacetate (n-DPA) selectively increasing the GABA level in the nerve terminals was studied in experiments on cats in comparison with diazepam effect. The changes in the spectrum of emotional-behavioral reactivity were estimated. In doses of 50 and 200 mg/kg n-DPA caused a marked antiphobic effect which was not accompanied by the activating component characteristic of diazepam. The n-DPA-induced increase in the GABA level in the nerve terminals is suggested to be important for the development of the anxiolytic effect of tranquilizers. The total increase in the GABA level in the nerve terminals is suggested to be important for the development of the anxiolytic effect of tranquilizers. The total increase in the GABA content in the brain correlates to a greater extent with the sedative effect of drugs.     

Role of neutrophils in the regulation of the reproductive tract microbiocenosis in women

The influence of neutrophils and their secretory products on the microflora of the vaginal contents in healthy women and in women having dysbiotic processes in the vagina was studied. The secretory products of neutrophils were found to produce a bactericidal effect on the representatives of the opportunistic bacteria, this effect being less pronounced with respect to lactic-acid bacteria. The established effect of neutrophils on bacteria is regarded as one of the mechanisms of microbiocenosis formation, ensuring colonization resistance.     

Potentiation of the gastro-protective effect of sulglicotide in the presence of cimetidine in the rat

The effects of sulglicotide, alone or combined with cimetidine, have been investigated on mucosal lesions induced in rats by pylorus ligation. In the same animals, the measurement of acid and pepsin output and of soluble and barrier mucus has been performed. Dose-dependent sulglicotide prevented the development of mucosal lesions and its protective effect was achieved without significant modifications in gastric acid secretion. The secretion of pepsin and of mucus was markedly inhibited at every dosage of the compound. Neither the damage to gastric mucosa nor the secretion of acid, pepsin and mucus were affected by cimetidine. The combination of the highest doses of both compounds resulted in a synergistic gastro-protective effect, not dependent on a synergistic effect on the reduction in acid secretion.     

Participation of the estradiol receptor in the hormonal inhibition of cyclic nucleotide phosphodiesterase in the uterus

The role of estradiol receptor was studied in the inhibitory effect of hormone on the cyclic nucleotide phosphodiesterase from immature Wistar rat uterus. It was shown that the preparative separation of the enzyme and hormone receptor by ultracentrifugation in isokinetic sucrose density gradient results in a 2.5-3-fold decrease of the estradiol effect on phosphodiesterase. This effect is completely restored after adding the separated estradiol receptor to the phosphodiesterase devoid of it. The effect of estradiol on the phosphodiesterase activity depends on a degree of receptor component aggregation: the action of estradiol on the enzyme intensities after transformation of receptor into the dissociated form (4S) and removes in the presence of the receptor component associated form (8S).     

The role of energy substrates in the regulation of force-frequency relationship in the rat myocardium: the influence of ambiocor

The effect of ambiocor (15 mg/100 ml), which contains natural substrates of energy metabolism, on the contractility of papillary muscle of the right ventricle of rat heart was studied at stimulation frequencies from 0.1 to 3.0 Hz at a temperature of 30 ± 1°C (n = 7). The effect was recorded 20 min after the addition of the preparation. It was demonstrated that ambiocor causes a significant (about 70%), independent of stimulation frequency, suppression of the amplitude of isometric contractions (negative inotropic effect), which is coupled with an increase in the relative value of the rest potentiation effect (a qualitative index of calcium content in SR). The influence of the mixture leads to significant alterations in the time parameters of the “contraction-relaxation” cycle: an increase in the duration of latent period; and a decrease in the time to peak tension and half-relaxation time. The effect of the mixture is partially reversible. During washing off the preparation with the control solution, the qualitative indicators of the contractile activity of papillary muscle are substantially improved in comparison with the initial ones. The character of alterations allows one to assume that the effect of ambiocor in the papillary muscle of the rat heart is realized partly through the suppression of the activity of sarcolemmal calcium channels.     

Involvement of proteolytic enzymes in the lipotropic effect of the pituitary polypeptide hormones

The influence of proteinase inhibitors on the lipolytic effect of the pituitary polypeptide hormones and epinephrine in an isolated adipose tissue of rabbits and rats has been studied. Neither of proteinase inhibitors changed the basal rate of lipolysis. Trasylol, a serine proteinase inhibitor, suppressed completely growth hormone (GH) effect and partially reduced the effect of adrenocorticotropin (ACTH) and beta-lipotropin (beta-LPH) but did not change the effect of epinephrine. Bacitracin proved ineffective with regard to the effect of polypeptide hormones. Pepstatin, an acid proteinase inhibitor, partially blocked the stimulation of lipolysis by ACTH without affecting the effect of GH and beta-LPH. The influence of proteinase inhibitors on the ACTH effect in rat adipose tissue was similar to that found in rabbit tissue. The Trasylol-induced inhibition of the hormone-stimulated lipolysis decreased to a considerable extent after GH or ACTH incubation with rabbit plasma or partial GH digestion with pepsin. This decrease was not observed when plasma serine proteinases were blocked during GH incubation with plasma. The results demonstrate an involvement of some proteolytic enzymes in the realization of the polypeptide hormone lipolytic effect and permit to suppose the requirement of preliminary activation of the hormones by means of proteolytic modification.     

Neural mechanism of the antisecretory effect of peptide YY in the rat colon in vivo

The purpose of this work was to determine the mechanism of the antisecretory effect of peptide YY in the rat colon and whether this effect is physiological. In this prospect, doses of exogenous peptide YY producing physiological and supraphysiological plasma levels were intravenously infused in rats provided with colonic and jejunal ligated loops in vivo, under secretory stimulation by vasoactive intestinal peptide. Peptide YY decreased the secretory effect of VIP in a dose-related fashion. The effect of peptide YY was blocked or strongly decreased by tetrodotoxin, hexamethonium, idazoxan, haloperidol, and the sigma antagonist BMY 14, 802 in both the colon and jejunum. We conclude that peptide YY decreases water and electrolyte secretion in the colonic mucosa by a complex neural mechanism involving at least two neurons connected through a nicotinic synapse, alpha-2 adrenoceptors and sigma receptors, and that this effect can occur with physiological doses of peptide YY.     

The effect of mexamine on liver mitochondrial function in rats in vivo and in vitro from the aspect of the mechanisms of the pharmacological and radioprotective action of the protector

The polarographic study of the functional status (FS) of rat liver mitochondria subjected to the effect of mexamine in vivo and in vitro and the hypoxic hypoxia in vivo has revealed various FS changes displaying disconnecting and rotenone-like effects and posthypoxic activation. With a mexamine dose of 50 mg/kg in vivo the direct effect of the protector contributes considerably to the mitochondrial FS. Within a wide range of mexamine doses no relationship was found between the pattern of the mitochondrial FS change in the liver and the protective effect with respect to bone marrow.     

Participation of mast cell 5-hydroxytryptamine in the vasoconstrictor effect of neurotensin in the rat perfused hindquarter

Neurotensin (NT) (1 X 10(-8) - 1.5 X 10(-6) g ml-1) caused a transient, dose-dependent increase in perfusion pressure in the rat perfused hindquarter. The vasoconstrictor effect of NT was associated with a short-lived, dose-dependent release of histamine and 5-hydroxytryptamine (5-HT) in the hindquarter effluent. Compound 48/80, a classical mast cell secretagogue, also elicited a vasoconstrictor effect in, and release of histamine from, the rat hindquarter. The vasoconstrictor effect and the release of histamine and 5-HT evoked by NT were much smaller in hindquarters derived from rats pretreated with compound 48/80 for 4 days to cause mast cell depletion than in hindquarters derived from control rats. The mast cell inhibitor cromoglycate (4 mg ml-1) inhibited by about 50% the histamine releasing effect and vasoconstriction produced by the lowest concentrations of NT utilized. The histamine releasing effect of compound 48/80 was more sensitive to blockade by cromoglycate than that of NT. The steroidal antiinflammatory and antiallergic drug dexamethasone did not affect the histamine and 5-HT releasing effect of NT. The vasoconstrictor effects of NT, compound 48/80 and 5-HT were markedly reduced by the 5-HT receptor antagonist methysergide (1 X 10(-7) g ml-1). Histamine (1 X 10(-6) - 10(-4) g ml-1) evoked a decrease in perfusion pressure in hindquarters pre-exposed to noradrenaline. The results suggest the participation of mast cell 5-HT in the vasoconstrictor effect of NT in the rat perfused hindquarter.     

Changes in the development of spontaneous motility in chick embryos after the chronic administration of GABA

From the 4th to the 16th day of incubation, GABA was administered continuously to chick embryos in a mean dose of 9.04 +/- 0.98 mg/kg e.w./24 h. On the 17th day of incubation, spontaneous motility was evaluated from the frequency of spontaneous movements as resting motility and motility after the acute administration of GABA (100 mg/kg e.w.), bicuculline (1 mg/kg e.w.) and oxazepam (10 mg/kg e.w.). 1) The chronic administration of GABA reduced the spontaneous motor activity of the experimental embryos to 38.4-47.8% of the control value. To obtain this effect it was sufficient to administer GABA between the 4th and the 8th day of incubation. 2) The inhibitory effect of the acute administration of GABA in the experimental embryos was only half its effect in the controls. Conversely, the relative size of bicuculline activation of motility was distinctly greater in the experimental embryos, which were also significantly more sensitive to oxazepam. The results show that GABA has a dual effect during embryogenesis--a) an early effect between the 4th and 8th day of incubation causing a chronic debt in the development of spontaneous motor activity, and b) an inhibitory effect as a central transmitter, which begins to be manifested in embryonic spontaneous motility of chick embryos on about the 15th day of incubation.     

The role of proteolytic processes in the stimulation of lipolysis in the adipose tissue by somatotropin, adrenocorticotropin and beta-lipotropin

The influence of proteinase inhibitors on the lipotropic effect of somatotropic (STH), adrenocorticotropic (ACTH) and beta-lipotropic (LPH) hormones in adipose tissue was studied in vitro. The effect of STH was found to be completely dependent on the activity of tissue serine proteinases of trypsin and chymotrypsin types. The effect of LPH partly depended on serine proteinases of chymotrypsin type, whereas that of ACTH--on chymotrypsin and carboxylic proteinases. The effects of all the three hormones were also manifested during lysosomal proteolysis. The protease-dependent inhibition was specific for polypeptide hormones and was unobserved in the lipotropic effect of adrenaline. The inhibiting effect of serine proteinase inhibitors on hormones pretreated with blood plasma or proteinases was much weaker than on untreated hormones. In adipose tissue the early insulin-like effect of STH, unlike the late lipotropic effect, was independent of proteolysis. It was assumed that primary proteolysis plays a role in the activation of polypeptide hormones which is necessary for the manifestation of the lipotropic action.     

The usage of individual-oriented model in studies on the role of the maternal effect in the reproductive switch in Cladocera

An individual-oriented model of the population of Daphnia longispina, an abundant zooplankton species in lakes and temporary water bodies of the Palaearctic temperate zone, is described. The concept of the model is based on the growth and reproduction potential of an individual and its ability to switch from parthenogenesis to gamogenesis, which is determined by the life conditions of three successive generations. The model was used for testing hypotheses on the role of maternal effect in the population dynamics of Daphnia. Several important conclusions are made, including the verification of the importance of this phenomenon for the seasonal adaptations in crustaceans. The possibility of maternal effect accumulation in a series of successive generations probably increases the tolerance of populations to annual oscillations of environmental factors. The model affirms the role of the maternal effect, along with the interpopulational polimorphism, as a mechanism providing for the stability of biological systems at the species (population) level.     

Role of phosphate in the regulation of the Pasteur effect in Saccharomyces cerevisiae

The occurrence of the Pasteur effect in Saccharomyces cerevisiae in several conditions has been examined. In these conditions measurements of a series of metabolites potentially involved in the regulation of the effect were performed. These included, among others, adenine nucleotides, citrate, fructose 2,6-bisphosphate and phosphate. Only phosphate changed in a consistent way, increasing in anaerobiosis when the Pasteur effect occurred. It is concluded that, with the available data, only phosphate may be considered as a regulator of the Pasteur effect in this microorganism.     

Data on the role of the frontal cortex in vegetative behavior

A homeostatic conditional reflex (CR) was elaborated to the effect of repeated inhalations in rats of a gas mixture containing 8 percent oxygen. The effect of the conditional response was opposite to that of the unconditional one. After ablation of the frontal cortex, the conditional reaction disappeared. The repeated administration of 40 mg/kg of histamine resulted in a tolerance to the temperature lowering effect of histamine similar to the habituation. An injection of distilled water brought about dishabituation. Tolerance was not influenced by the ablation of the frontal cortex, but the dishabituating effect of distilled water was absent.     

Endogenous opioid system in the realization of the analgesic effect of alpha-tocopherol in reference to algomenorrhea

Beta-endorphin-like immunoreactivity was studied in 7 patients with algomenorrhea during pain attack and 15 minutes after alpha-tocopherol administration with a therapeutic aim (till the analgetic effect was reached). There was an increase in beta-endorphin-like immunoreactivity after alpha-tocopherol administration. Naloxone administration to 9 patients with algomenorrhea of various etiology resumed the pain. The effect of alpha-tocopherol application for pain relief depended on the pathogenesis of algomenorrhea. At the same time naloxone administration failed to resume the pain in patients, in whom alpha-tocopherol had a strong analgetic effect. It is assumed that the endogenous opioid system participates in alpha-tocopherol effect on pain relief in patients with algomenorrhea.     

The role of energy substrates in regulation of the force-frequency relationship in the rat myocardium: effect of ambiocor

The effect of ambiocor (15 mg/100 ml), which contains natural substrates of energy metabolism, on the contractility of papillary muscles (PM) of the right ventricle of the rat heart was studied at stimulation frequencies from 0.1 to 3.0 Hz at a temperature of 30 +/- 1 degrees C (n = 7). The effect was recorded 20 min after the addition of the preparation. It was demonstrated that ambiocor causes a significant (about 70%), independent of stimulation frequency, suppression of the amplitude of isometric contractions (negative inotropic effect), which is coupled with an increase in the relative value of the rest potentiation effect (a qualitative index of calcium content in sarcoplasmic reticulum). The influence of the mixture leads to significant alterations in the time parameters of the "contraction-relaxation" cycle: an increase in the duration of latent period; and a decrease in the time to peak tension and half-relaxation time (TR50%). The effect of the mixture is partially reversible. During the washing of the preparation with the control solution, the qualitative indicators of the contractile activity of papillary muscles are substantially improved in comparison with the initial ones. The character of alterations allows one to assume that the effect of ambiocor in the papillary muscles of the rat heart is realized partly through the suppression of the activity of sarcolemmal calcium channels.     

Adrenoceptor mechanisms in the cardiovascular effects of cocaine in conscious squirrel monkeys.

The purpose of the current experiment was to study the role of various adrenoceptor subtypes in the cardiovascular response to cocaine in conscious squirrel monkeys. A variety of adrenoceptor antagonists were administered i.v. prior to the administration of 0.3 mg/kg cocaine (i.v.). Cocaine alone produced an increase in both blood pressure and heart rate. The non-selective alpha adrenoceptor antagonist phentolamine produced a dose-dependent antagonism of the pressor effect of cocaine, as did the alpha-1 selective antagonist prazosin. The alpha-2 selective antagonist yohimbine had no effect on the pressor effect of cocaine. The non-selective beta antagonist propranolol enhanced the pressor effect of cocaine as did the beta-1 selective antagonist atenolol. However, the effect of atenolol was not dose-dependent. The beta-2 selective antagonist ICI 118,551 and labetalol, which blocks both alpha and beta adrenoceptors, did not alter the pressor effect of cocaine. Propranolol, atenolol, and labetalol all antagonized the tachycardiac effect of cocaine in a dose-dependent manner, while the beta-2 antagonist ICI 118,551 did not. Phentolamine, prazosin and yohimbine also reduced the tachycardiac effect of cocaine, although these effects were dose-dependent only for yohimbine, which also significantly elevated baseline heart rate. These results indicate that alpha-1 adrenoceptor mechanisms mediate the pressor effect of cocaine, while beta-1 adrenoceptor mechanisms are involved in the tachycardiac effect of cocaine in squirrel monkeys. Propranolol potentiated cocaine's pressor effect through beta-2 independent mechanisms. Thus, neither alpha-2 nor beta-2 adrenoceptor mechanisms appear to be involved in cocaine's cardiovascular effects.     

Effect of heparin on the reactivity of SH-groups in the macrophage membrane

The effect of heparin on macrophage (M phi) adherence and on the reactivity of membrane SH-groups to the specific SH-oxidizing agent 4,4'-dithiodipyridine (PDS) was studied. Various types of SH-reactive agents, except 5,5'-dithio-bis (2-nitrobenzoate) (DTNB), were found to inhibit adherence of mouse peritoneal M phi to serum-coated Falcon surfaces. Heparin inhibited M phi-adherence in serum containing medium and in higher concentrations stimulated the adherence inhibitory effect of PDS, especially in Ca-depleted medium. This effect of heparin may be due to its polyanionic character, as dextran sulphate but not dextran induced similar changes. The effect of heparin to increase the sensitivity of membrane SH-groups against SH-reactive agents was demonstrated also by cytotoxicity experiments. It is concluded that heparin makes the M phi-membrane unstable, by exposing some hidden SH-groups playing a role in membrane function.     

Studies on the Effect of Vitamins in the Animals under the Cold

Some evidences have indicated that the cold environmental temperature has a depressing effect on growth and the vitamin A contained in the kidney of rats. The supplement of the vitamin A revealed to counteract the depressing effect on growth.     

Role of the striatum in the influence of serotoninergic substances on the course of corazole seizures in rats]

The effect of 5-oxytryptophane (5-OT) and of parachlor-phenylalanine (pCPA) on the behaviouristic EEG manifestations of metrazol convulsions in electrostimulation and destruction of the striatum was studied. The effect of the preparations on the myoclonia and the spike-wave rhythm caused by metrazol did not largely depend on the functional condition of the corpus striatum. The capacity of 5-OT to facilitate, and of pCPA to aggravate the course of generalized convulsions and of the postconvulsive state became enhanced in stimulation and was eliminated after the destruction of the striatum.