Picrotoxin effects on frog ERG at different background illumination but same stimulus contrast

The effect of blockade of GABAergic synapses by picrotoxin on the b- and d-wave of frog ERG was investigated under scotopic (0.002 lx), mesopic (2 lx) and photopic (200 lx) background illumination (Ib). Diffuse white stimuli with two levels of contrast (0.5 and 2.5) were used with each Ib. The aim was to compare the effects of picrotoxin at different background levels, but same stimulus contrast. We found that picrotoxin markedly increased the amplitude and rate of rise of the leading edge of the b- and d-wave with each Ib. This effect was most pronounced at mesopic Ib, smaller at photopic Ib and least pronounced at scotopic Ib. It was relatively stronger on the d-wave than on the b-wave amplitude under scotopic and mesopic conditions. Under photopic conditions, the difference between the picrotoxin effect on the b- and d-wave was much smaller. The possible neuronal mechanisms of the above described picrotoxin effects are discussed.     

Comparative studies on the effects of some enkephalin agonists on the ERG of frog and turtle

1. Effects of mu-agonist morphine in a concentration of 1.10(-5)-1.10(-6) M and delta-agonist Dalargin in a concentration of 1.10(-5)-1.10(-8) M on electroretinogram (ERG) of frog (mixed type of retina) and turtle (predominantly cone retina) were investigated. 2. The enkephalin agonists studied influenced both types of retina in a different manner, producing mainly inhibitory effects. 3. Variability in mu-receptors sensitivity in the turtle retina, most probably depending on the seasons, was observed. 4. The data obtained show that opiate-sensitive mechanisms control the bioelectric activity of the distal layers of frog and turtle retina. 5. Species specificity and variability in sensitivity of the opiate receptors are discussed.     

Effects of benzodiazepines on central serotonergic mechanisms.

If the rat conflict test were a valid animal model of anxiety neurosis, evidence which implicates serotonin systems in the anxiety-reducing actions of benzodiazepine tranquilizers could be summarized as follows: (1) The punishment-lessening effects of benzodiazepines in the conflict test are mimicked by serotonin antagonists (methysergide, cinanserin, bromolysergic acid), serotonin synthesis inhibition (PCPA), and serotonin nerve terminal damage (5,6-dihydroxytryptamine). (2) Punishment effects may be intensified by the serotonin precursor, 5-hydroxytryptophan (in combination with a monoamine oxidase inhibitor), serotonin agonists (alpha-methyltryptamine), or intraventricular injections of serotonin itself. Intraventricularly administered serotonin also antagonizes the punishment-lessening effects of benzodiazepines. (3) Stimulation of the serotonergic cell bodies in the dorsal raphe nucleus by local application of crystalline carbachol causes intense suppression of behavior. The suppressive effects of raphe stimulation are antagonized by systemic administration of benzodiazepines. (4) In biochemical experiments, the decrease in norepinephrine turnover induced by oxazepam rapidly undergoes tolerance, whereas the decrease induced in serotonin turnover is maintained over repeated doses. These results parallel findings in the conflict test which indicate that the depressant action of oxazepam rapidly undergoes tolerance, whereas the anxiety-reducing action is maintained over repeated doses. Although central serotonin neurons are thus implicated in the therapeutic actions of benzodiazepine tranquilizers, it is quite possible that the drugs actually act indirectly to reduce serotonin activity. The concept that benzodiazepines may exert a primary action on GABA-containing neurons, which in turn regulate serotonergic transmission, was supported by preliminary psychopharmacological evidence. The GABA-antagonist picrotoxin, at doses that do not disrupt unpunished behavior, fully antagonizes the punishment-lessening effects of benzodiazepines in the conflict test.     

Effects of ethimizol on frog neuromuscular junction

The effects were studied of ethimizol, a substance activating memory processes, on features of synaptic transmission during experiments on frog cutaneous pectoris muscle. It was found that the presynaptic action of ethimizol consists of raising the frequency of miniature potentials, when used at a concentration of 0.5–10 mM, and modulating quantal content of synaptic transmission due to changes in binomial quantal release parameters p and n when 0.5–2 mM ethimizol was used. This substance facilitated transmission at synapses with a low initial level of transmitter release. This substance facilitated transmission at synapses with a low initial level of transmitter release. Ethimizol was also found to have a postsynaptic action, consisting of reducing amplitude at a concentration of 5–10 mM and prolonging synaptic currents and potentials when concentrations of 0.5–10 mM were used. The latter effect produced a considerable increase in the time integral of endplate potentials. The postsynaptic action of ethimizol is perhaps seen in its effects on features of postsynaptic ionic channels. The effects of ethimizol are discussed with a view to how it may act within the central nervous system as a nonspecific modulator.A. A. Zhdanov Leningrad State University. Translated from Neirofiziologiya, Vol. 17, No. 6, pp. 757–763, November–December, 1985.     

Effects of barium on isolated frog spinal cord

The effects of Ba2+ were studied in vitro on the isolated frog spinal cord. Ba2+ (25 microM-5 mM) caused a concentration-dependent depolarization of ventral (VR) and dorsal (DR) roots. TTX and Mg2+ substantially reduced the depolarization suggesting that interneuronal effects were involved. Ba2+ (25-500 microM) markedly increased the frequency and duration of spontaneous VR and DR potentials and substantially enhanced the duration (and frequently the amplitude) of VR and DR potentials evoked by DR stimulation. Higher concentrations of Ba2+ (1-5 mM) reduced both spontaneous and evoked potentials. Ba2+ (25-500 microM) enhanced the amount of K+ released by a DR volley and by application of L-glutamate and L-aspartate. The cation reduced VR and DR root depolarizations produced by elevated [K+]0. VR potentials induced by L-glutamate, L-aspartate, GABA and glycine and DR depolarizations caused by GABA were reduced by Ba2+. These results show that Ba2+ has complex actions on reflex transmission, interneuronal activity, the postsynaptic actions of excitatory and inhibitory amino acids and the evoked release of K+.     

Effects of monensin on photoreceptors of isolated frog retinas

Monensin induces the vacuolization of the Golgi apparatus in photoreceptors of isolated frog retinas and also, more slowly, produces a vacuolization of the pre-synaptic terminals. Accompanying these effects is an inhibition of transport of protein to the outer segment so that the radioactive bands normally detectable by autoradiography do not form. Monensin thus promises to be a useful tool in the study of intracellular transport in photoreceptors. The findings reported here indicate that impairment of the functioning of the Golgi apparatus considerably diminishes transport of membrane protein to the rod outer segment suggesting that passage through the Golgi apparatus is an obligatory step for completion of outer segment membrane or its transport to the outer segment.     

Effect of 2-amino-4-phosphonobutyrate on the OFF responses of frog retinal ganglion cells and local ERG after glycinergic blockade

Perfusion with the ON channel blocker 2-amino-4-phosphonobutyrate (APB) of dark adapted frog eyecups not only abolished the ganglion cells' (GC) ON responses and the ERG b-wave, but markedly potentiated the OFF responses of ON-OFF and phasic OFF-GCs and the d-wave amplitude of simultaneously recorded local ERG. Glycinergic blockade by strychnine prevented this potentiating effect in 31 out of 69 GCs, but did not change it at all in the other cells. At the same time the d-wave potentiation was preserved during the glycinergic blockade in all eyecups. The results indicate that glycinergic transmission is involved in the inhibition exerted from ON upon OFF channel in some but not all frog retinal GCs.     

Effects of anti-cholinoceptor antibodies on the frog heart]

Research on isolated hearts of Rana temporaria has shown that upon treating them with anti-cholinoreceptor antibodies, there occurs a considerable reduction of inhibition effect on cardiac activity of acetylcholine or carbacholine. A reduction of inhibition effect was noticed after incubation of frog's heart with antibodies against cholinoreceptors obtained from motor-denervated muscles of frogs as well as from muscles of mice Balb/c. Cholinoreceptor protein was obtained and purified by A. Sobel's method. Control tests were made with serum of non-immunized rabbits and rabbits immunized with material obtained from non-denervated muscles of frogs. It was concluded that acetylcholinoreceptor antibodies are capable of provoking atropine-like effect on frog's heart. According to our data, anti-cholinoreceptor antibodies as well as cholinoreceptors are relatively non-specific to species.     

Effects of ouabain on frog gastric mucosa in vitro

The effect of the addition of ouabain to the nutrient solution was determined on resistance, potential difference (p.d.) and H⁺ secretion rate. In NaCl media, 10^?3 M ouabain decreased significantly the p.d. from 25.6 mV to 16.1 mV in 30 min and to 11.0 mV in 60 min. NO significant changes occurred in resistance and H⁺ secretion rate. In Na₂SO₄ (Cl^?-free) media, ouabain produced a biphasic effect on p.d. The p.d. changed from ?28.0 mV (nutrient-negative) to a nadir of ?37.4 mV in 7 min and then increased to ?16.4 mV in 60 min. At the nadir there was no significant change in resistance or H⁺ secretion rate but at 60 min, unlike Cl^? media, resistance increased by 36% and H⁺ secretion rate decreased by 43%. To decide whether the ouabain-caused decrease in H⁺ rate in Na₂SO₄ media was due to an effect on the H⁺ pump or on resistance of the return pathways, the voltage was clamped at 0 and 40 mV. Clamping the voltage showed that in the case of a marked decrease in the H⁺ secretion rate, the H⁺ transport mechanism itself was inhibited (and not the parallel pathway). The decrease in p.d. due to ouabain in Cl^? and SO₄^2? media indicates that the (Na⁺ + K⁺)-ATPase mechanism may be electrogenic.     

Effects of benzodiazepines on single unit activity in the substantia nigra pars reticulata

Intravenous administration of two benzodiazepines, flurazepam and diazepam, had an inhibitory effect on the firing rates of neurons of the substantia nigra pars reticulata, a brain region with an identified GABAergic innervation. Diazepam was more potent than flurazepam. Bicuculline and picrotoxin, two drugs which block GABAergic transmission, and caffeine and theophylline, two methylxanthines which inhibit benzodiazepine binding, all reversed the inhibition produced by diazepam. The action of theophylline was less consistent than that of caffeine. Similarly, Ro 15–1788, an imidazodiazepine which putatively functions as a specific benzodiazepine antagonist, reversed the diazepam-induced inhibition. These findings are consistent with previous reports which suggest that the benzodiazepines may act through a GABAergic mechanism. In a separate group of experiments, caffeine or Ro 15–1788 was administered alone. While caffeine excited all reticulata cells tested. Ro 15–1788, the more specific benzodiazepine antagonist, generally had little excitatory effect. These results suggest: 1) that cells of the substantia nigra pars reticulata may not receive a substantial, tonic inhibition mediated by an endogenous benzodiazepine-like substance; and 2) that the methylxanthines may increase reticulata cell firing, at least in part, through mechanisms unrelated to the blockade of benzodiazepine receptors.     

Effects of insulin on thyrotropin releasing hormone from frog skin

Thyrotropin releasing hormone (TRH) is concentrated in the skin of Rana nigromacula. Its elution profile on Sephadex G-10 was identical to that of synthetic TRH. Insulin and noradrenaline stimulated TRH release from frog skin in a dose-related manner. The effects of insulin were not blocked by preincubation with phentolamine and they enhanced the noradrenaline effect. These data indicate that insulin stimulates directly TRH release from frog skin in other than the sympathetic pathway.