A clinico-physiological study of the mechanism of the cholecystokinetic action of medicinal mineral waters of the naftusia type]

It is stated that the cholecystokinetic action of curative waters of naftusia type is due to the interaction of its organic substances, particularly bitumens, with mucous membrane of gastroduodenal zone by the intramural reflex mechanism with participation of humoral factor. It is indicated by attenuation or suppression of the effect by pharmacons interrupting the work of interchemoreception, N- and M-cholinoreceptors, beta-adrenoreceptors; intensification of the effect by blockade of alpha-adrenoreceptors; its reversion by nonselective stimulation of adrenoreceptors; release of gastrin, glucagon and insulin into blood.     

Thrombolytic agents of the preparation from the medicinal leeches

The thrombolytic effect of an extract from medicinal leeches orally administered to rats was shown. This effect depends on the number of administrations and on the concentration of extract. It is due to the leech prostaglandins and enzyme destabilase. After the extraction of prostaglandins by ethylacetate the thrombolytic effect diminished by 45%. It is supposed that the leech-prostaglandins, like prostacyclin and its stable analogous, induce the release of tissue plasminogen activator from vessel walls. The thrombolytic effect of destabilase was demonstrated in experiments in vitro. We observed the phenomenon of increasing of glutaminase activity of citrate blood and the appearance of amidolytic and destabilase activity.     

Effect of the opiate antagonist naloxone on the electrical activity of identified neurons in the edible snail

The opiate antagonist naloxone modifies the electric activity of some identified neurons of the Helix lucorum which have not been preliminary exposed to the effect of exogenous opioids. Some neurons are excited while others are inhibited by naloxone, and in both cases the reaction may have both a short and long latent period. The reactions depend on naloxone dose and become less expressed or are blocked when naloxone is administered together with the agonists of opiate receptor (morphine, D-Ala2, D-Leu5-enkephalin, bremazocine and beta-endorphin). Opioids alone do not produce any effect on neurons. The effect of naloxone on neurons is assumed to be a result of the elimination by the opiate antagonist of the tonic effect of endogenous opioids by their replacing on opiate receptors which are constantly stimulated by endogenous ligands.     

Hofmeister effect underlying the quiescence of sperm motility in the vas deferens of the viviparous guppy Poecilia reticulata

Guppy sperm are immotile in the fluid (seminal plasma) of the vas deferens. We previously reported that the initiation of sperm motility is regulated by "Hofmeister solutes" in the isotonic medium. This indicates that chaotropes in solution activate the guppy sperm, whereas counteracting kosmotropes negate this activational effect and keep the sperm immotile. Here we show that seminal plasma has a strong inhibitory effect on sperm activation in response to chaotropes and multivalent ions, and that this inhibitory effect is due to kosmotropicity of the seminal plasma. These findings suggest a novel system of regulation of sperm motility in the guppy, a viviparious fish, in which the sperm are kept immotile in the vas deferens by a physicochemical effect (the Hofmeister effect) of the seminal plasma.     

The role of the ADP/ATP-antiporter in the inhibition of nonspecific permeability of the inner mitochondrial membrane by cyclosporin A

The effect of the conformational state of the ADP/ATP-antiporter on the efficiency of inhibition by cyclosporine A of the Ca(2+)-induced increase of nonspecific permeability of the inner mitochondrial membrane was under study. It was found that the ADP/ATP-antiporter inhibitor carboxyatractyloside is able to reverse the cyclosporine A-induced inhibition of this nonspecific permeability. The effect of carbocyatractyloside is manifested only in mitochondria depleted of adenine nucleotides. The bifunctional SH-reagent phenylarsine oxide is also able to reverse the cyclosporine A effect. The data obtained testify to the fact that inhibition by cyclosporine A of nonspecific permeability is due to its effect on the conformational state of the ADP/ATP-antiporter.     

III - Prostaglandin hyperalgesia: Relevance of the peripheral effect for the analgesic action of opioid-antagonists

Morphine injected into the rat cerebral ventricles had a marked analgesic effect, while no effect was observed with pentazocine and naloxone or nalorphine caused a strong hyperalgesia. Administered systemically (IP) naloxone and nalorphine caused a transitory analgesia followed by a long lasting hyperalgesic effect; morphine and pentazocine showed only an analgesic effect. It was concluded that the site of analgesic action of opioid-antagonists is peripheral rather than central. The peptidase-resistant enkephalin-analog, BW 180c, which does not cross the blood brain barrier, caused a marked analgesia by IP administration to paws made hyperalgesic by PGE₂ or carrageenin. It is suggested that agents derived from morphine, morphine-antagonists, enkephalins or cGMP devoid of central effect but having a strong peripheral effect may constitute a new class of safer analgesics.     

Characterization of the histamine releasing effect of neurotensin in the rat heart

Bolus injections of neurotensin (NT) in the rat perfused heart elicited a transient, dose-dependent histamine release. The histamine releasing effect of NT appears to be independent of the heart rate and coronary perfusion pressure and it was not influenced by atropine, propanolol, prazosin, methysergide, ketanserin, indomethacin, morphine, lidocaine or by removal of the atria. However, it was potentiated by adenosine, inhibited by sub-stimulatory concentrations of NT and the mast cell membrane stabilizing drug cromoglycate but was unaltered by the calcium antagonist verapamil. The absence of calcium in the heart perfusate suppressed the histamine releasing effect of NT. These results suggest that the histamine releasing effect of NT in the rat heart results from a direct effect on ventricular mast cells and is calcium-dependent.     

III - Prostaglandin hyperalgesia: relevance of the peripheral effect for the analgesic action of opioid-antagonists

Morphine injected into the rat cerebral ventricles had a marked analgesic effect, while no effect was observed with pentazocine and naloxone or nalorphine caused a strong hyperalgesia. Administered systemically (IP) naloxone and nalorphine caused a transitory analgesia followed by a long lasting hyperalgesic effect; morphine and pentazocine showed only an analgesic effect. It was concluded that the site of analgesic action of opioid-antagonists is peripheral rather than central. The peptidase-resistant enkephalin-analog, BW 180c, which does not cross the blood brain barrier, caused a marked analgesia by IP administration to paws made hyperalgesic by PGE2 or carrageenin. It is suggested that agents derived from morphine, morphine-antagonists, enkephalins or cGMP devoid of central effect but having a strong peripheral effect may constitute a new class of safer analgesics.     

Interference by the mantispid Mantispa uhleri with the development of the spider Lycosa rabida

Abstract. 1. The larvae of Mantispa uhleri Banks (Neuroptera: Mantispidae) board spiders to await the production of an egg sac containing their obligate developmental food. While aboard the spider, larvae maintain themselves by feeding on spider blood. This parasitic behaviour was investigated by allowing larvae to board sixth instar Lycosa rabida Walckenaer (Araneae: Lycosidae). Larval parasitism has a direct and indirect effect on the developmental physiology of the spider.
2. The direct effect, equal in both spider sexes, is an increase in development time and a decrease in adult size.
3. The indirect effect on development time and adult size is brought about by the loss of an instar in female spiders only. Parasitized females were mature at nine or ten instars; control females at ten or eleven. Male instar number was not affected; both control and parasitized males were mature at nine or ten instars.
4. The net result is that parasitized female spiders are even smaller than would be predicted from the direct effect alone, but actually mature faster than control females. In males there is only the direct effect. The adaptive significance of this sexually dimorphic response is discussed.     

Effects of glutamic acid and glutathione on the secretory function of the stomach

Experiments on dogs with Pavlov isolated pouches and gastric fistulas have shown that the ingested solution of MSG produces a potentiating effect on maximal gastric secretion caused by pentagastrin. This effect is apparently connected with the formation of glutathione in intestine. The glutathione concentration in blood after the intake of MSG is significantly elevated. It has been established that reduced glutathione administered in blood produced the similar potentiating effect on gastric secretion caused by pentagastrin.     

Mechanism of the inhibiting effect of the Cu-tyrosine complex on the hydroxylation reactions

The Cu-tyrosine complex, a low molecular weight analog of superoxide dismutase, exerts an inhibiting effect on cytochrome P-450. The inactivation of cytochrome Y-450 with its transition to cytochrome Y-420 can cause the inhibition by the Cu2+ - Tyr2 complex of dimethylaniline N-demethylation and p-nitroanisol O-demethylation. In case of p-hydroxylation of aniline the inhibiting effect of the Cu-tyrosine complex is much more pronounced than its inactivating effect on cytochrome P-450. In the presence of albumin the complex produced no inactivating effect on cytochrome P-450; under these conditions the inhibiting effect of Cu2+ - Tyr2 on N- and O-demethylation is removed. In case of aniline p-hydroxylation albumin partly decreases the inhibiting effect of the complex on this reaction. In a soluble system containing isolated cytochrome P-450 and cumole hydroperoxide only the aniline p-hydroxylation reaction was found sensitive to the effect of superoxide dismutase. The data obtained suggest participation of the superoxide radical only in aniline p-hydroxylation but not in the reactions of N-demethylation of dimethylaniline and O-dealkylation of p-nitroanisol.     

The effect of previously infested spruce needles on the growth of the green spruce aphid, Elatobium abietinum, and the effect of the aphid on the amino acid balance of the host plant

The effect of chlorosis induced in needles of Sitka and Norway spruce by the green spruce aphid on growth of the aphid is investigated, and the effect of infestation of the aphid on amino acid levels in Sitka spruce foliage is reported. On both Sitka and Norway spruce green spruce aphids were heavier when reared on chlorotic (previously infested) needles than when reared on green (previously uninfested) needles. The effect was more pronounced on Sitka than on Norway spruce. Infestation of the aphid altered the amino acid balance of Sitka spruce foliage but not the concentration of total amino acids. Possible causes of chlorosis, the influence of individual amino acids on aphid growth, the potential effect of chlorosis on outbreaks of the aphid and the differences in susceptibility of Sitka and Norway spruce to damage by the aphid are discussed.     

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 arginine in the stabilization of proteins against aggregation

The amino acid arginine is frequently used as a solution additive to stabilize proteins against aggregation, especially in the process of protein refolding. Despite arginine's prevalence, the mechanism by which it stabilizes proteins is not presently understood. We propose that arginine deters aggregation by slowing protein-protein association reactions, with only a small concomitant effect on protein folding. The associated rate effect was observed experimentally in association of globular proteins (insulin and a monoclonal anti-insulin) and in refolding of carbonic anhydrase. We suggest that this effect arises because arginine is preferentially excluded from protein-protein encounter complexes but not from dissociated protein molecules. Such an effect is predicted by our gap effect theory [Baynes and Trout (2004) Biophys. J. 87, 1631] for "neutral crowder" additives such as arginine which are significantly larger than water but have only a small effect on the free energies of isolated protein molecules. The effect of arginine on refolding of carbonic anhydrase was also shown to be consistent with this hypothesis.     

Dual effect of insulin-like growth factor on the apical 70-pS K channel in the thick ascending limb of rat kidney

We used the patch-clamp technique to study the effect of insulin-like growth factor I (IGF-I) on the apical 70-pS K channel in the isolated thick ascending limb (TAL) of the rat kidney. The isolated TAL was cut open to gain access to the apical membrane. Addition of 25 nM IGF-I stimulates the apical 70-pS K channel and increases channel activity, defined by the product of channel open probability and channel number, from 0.31 to 1.21. The stimulatory effect of IGF-I is not mediated by nitric oxide- or protein tyrosine phosphatase-dependent mechanisms, because inhibition of nitric oxide synthase or blocking protein tyrosine phosphatase did not abolish the stimulatory effect of IGF-I on the 70-pS K channel. In contrast, inhibition of mitogen-activated protein (MAP) kinase with PD-98059 or U0126 abolished the stimulatory effect of IGF-I. This suggests that MAP kinase is responsible for mediating the effect of IGF-I on the apical K channels. Moreover, the effect of IGF-I on the apical 70-pS K channel is biphasic because high concentrations (>200 nM) inhibit apical 70-pS K channels. Application of 400 nM IGF-I decreased channel activity from 1.45 to 0.2. The inhibitory effect of IGF-I is not blocked by calphostin C (an inhibitor of PKC), but inhibition of protein tyrosine kinase with herbimycin A abolished the IGF-induced inhibition. We conclude that IGF-I has a dual effect on the apical 70-pS K channel in the TAL: low concentrations of IGF-I stimulate, whereas high concentrations inhibit the channel activity. The stimulatory effect of IGF-I is mediated by a MAP kinase-dependent pathway, whereas the inhibitory effect is the result of stimulation of protein tyrosine kinase.     

On the structural specificity in the regulation of the hydroxymethylglutaryl-CoA reductase and the cholesterol-7 alpha-hydroxylase in rats. Effects of cholestanol feeding

The effect of feeding 2% cholestanol or cholesterol on cholesterol-7 alpha-hydroxylase activity and hydroxymethylglutaryl (HMG)-CoA reductase activity was studied in rats. The rate of 7 alpha-hydroxylation of a trace amount of labelled cholesterol increased by about 80% after the cholestanol feeding, whereas the 7 alpha-hydroxylation of endogenous microsomal cholesterol increased by about 40%. The latter conversion was measured with an accurate technique based on isotope dilution-mass spectrometry. After cholesterol feeding, the corresponding figures were about 50 and 60%, respectively. The cholestanol feeding had no significant effect on the HMG-CoA reductase activity, whereas the cholesterol feeding decreased the activity by about 80%. From the results obtained, it is concluded that the increased 7 alpha-hydroxylation observed after cholesterol feeding can not be explained only by a simple expansion of the substrate pool. The similar effect of both cholesterol and cholestanol on the cholesterol 7 alpha-hydroxylase activity and the diverging effect on the HMG-CoA reductase activity show that there is no coupling between cholesterol synthesis and degradation under the conditions employed. The lack of effect of cholestanol on the HMG-CoA reductase activity indicates a high structural specificity of the receptor involved in regulation of the enzyme. If a receptor mechanism is involved in the stimulation of the cholesterol-7 alpha-hydroxylase by cholesterol and cholestanol, these receptor(s) must be different from those involved in the regulation of the HMG-CoA reductase.     

Differences in the mechanism of the antihypoxic action of benzodiazepine receptor agonists and muscimol

Neuropharmacological analysis of previously revealed antihypoxic activity of benzodiazepines (BDZ) has been performed in experiments on mice exposed to hypoxia. Antihypoxic effect of diazepam is shown to be antagonized by the central BDZ receptor blocker, Ro 15-1788. A certain degree of antihypoxic activity also abolished by Ro 15-1788 is exhibited by hypothetical ligands of BDZ receptors: inosin, nicotinamide, ethyl-beta-carboline-3-carboxylate. The effect of dipyridamole, a drug with high affinity for BDZ receptors of the peripheral type is not antagonized by Ro 15-1788, another evidence of Ro 15-1788 affinity precisely to the central BDZ receptors. GABA-mimetics (muscimol and GABA cetyl ester) were also found to have marked antihypoxic activity. Unlike BDZ receptor agonists, this effect is reduced by bicuculline and not by Ro 15-1788. The data obtained suggest that antihypoxic activity of BDZ is caused by their direct interaction with the central BDZ receptors, probably with the type which is not modulated by GABAA receptors.     

Effect of mineralocorticoids on the Na, K-ATPase activity of the rat brain

The effect of desoxycorticosterone (DOC) on Na, K-ATPase activity was studied in vivo and in vitro on microsomal rat brain fractions. An hour after intramuscular administration of DOC a noticeable increase in the enzyme activity was observed. Preincubation of microsomal brain fractions with 5 and 15 mkg/ml of DOC caused a decrease in Na, K-ATPase activity, with the results evident 3-5 minutes after the addition of the hormone into the incubation medium. The idea of a two-phase hormonal effect is suggested. It is likely that desoxycorticosterone effect is realized both by the direct influence, on Na, K-ATPase of the brain plasma membrane and by the influence on the biosynthesis.