Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology最新文献

The behavior of a blue-green alga, Phormidium sp., against inorganic arsenic dissolved in media was studied. The Phormidium sp. was shown to have capabilities of endurance against a high concentration stress of arsenic and of accumulation of arsenic. Studies on excretion of arsenic by the alga showed that there were two excretion modes, each of which had a characteristic rate constant and it could be attributed to two types of binding situations between arsenic and the tissues of the alga. The arsenate absorbed by the algae was readily reduced to arsenite within their tissues.

In vitro addition of cadmium chloride (CdCl2) or nickel chloride (NiCl2) to an incubation mixture produced a concentration-dependent inhibition of liver microsomal aniline 4-hydroxylase activity of male guinea-pig. The inhibitory effect of CdCl2 on the enzyme activity was stronger than that of NiCl2. While CdCl2 also caused a concentration-dependent inhibition of liver microsomal ethylmorphine N-demethylase activity, NiCl2 increased the enzyme activity between the concentrations 10(-5) and 10(-3) M and caused a rather abrupt decline at higher concentrations. When the liver 10,000 g supernatants were preincubated in the presence of metals, metal-induced inhibitions increased as the time of preincubation progressed and attained their maximal rates at about 5 and 15 min for microsomal aniline 4-hydroxylase and ethylmorphine N-demethylase activities, respectively. However, no change was noted by NiCl2 on liver microsomal ethylmorphine N-demethylase activity as the time of preincubation progressed. After preincubations, the concentration-dependent inhibitions produced by metals on liver microsomal drug metabolizing enzyme activities were found to be stronger and in favour of CdCl2.

Relaxation of catch tension by 8-bromo-cyclic GMP in the ABRM of Mytilus was blocked in the presence of mersalyl and was markedly reduced after treatment of the muscle with alpha-methyldopa. In the muscle depolarized by 540 mM KCl + 5 mM EGTA solution, 8-bromo-cyclic GMP could not relax Ca-contracture. Hexylamine and phenylethylamine, which are assumed to relax the catch acting on relaxing nerve terminals, could not relax the contracture either. Serotonin and dopamine, which are known to relax the catch acting directly on the muscle fibre membrane, could relax it. In the muscle depolarized by 250 mM KCl + 5 mM EGTA solution, all of the cyclic nucleotides tested (cyclic AMP, cyclic GMP and their analogues), serotonin and dopamine relaxed Ca-contracture, but hexylamine and phenylethylamine did not relax the contracture. The possibilities of the involvement of cyclic GMP in the presynaptic and postsynaptic relaxing mechanisms in the ABRM are discussed.

Studies using clorgyline, deprenyl and semicarbazide as inhibitors showed that carp heart homogenate contained a new type of monoamine oxidase (MAO) and a clorgyline- and deprenyl-resistant amine oxidase (CRAO). The deamination of monoamines by carp heart MAO proceeded in two steps by a double-displacement (ping-pong) mechanism. The Km values of the MAO for oxygen (K0 values) with tyramine, 5-hydroxytryptamine (5-HT) and beta-phenylethylamine (PEA) as substrates were identical (59 microM).

Using split fin preparations of a tilapia, Sarotherodon niloticus, release of ATP from the adrenergic melanosome-aggregating nerve was studied. Associated with the melanosome aggregation, an apparent release of ATP was detected following electrical nervous stimulation. ATP-release increased with increases in stimulus intensity. Spontaneous release of a small amount of ATP was also detected. It was concluded that ATP may be liberated as a co-transmitter along with the true one, norepinephrine, and it may function to help melanophores recover from the effect of the latter, thus enabling fish to change their hue very rapidly.

The effect of the insecticide Decamethrin on ionic transport through the isolated skin of Rana esculenta was studied; the skins were bathed with 1-2 mEq Na2SO4 or choline-Cl solutions (exterior), and with Ringer normal (interior). Under open circuit (OC) conditions, mucosal Decamethrin (10(-6) M), did not provoke changes in Na+ fluxes. At 10(-5) M there was a slight inhibition of the JoNa+ after 30 min. The Cl- fluxes did not change. With longer treatments (60-90 min, OC, 10(-5) M) the JnNa+ was inhibited; at 10(-4) M it was augmented. The JnH+ was not affected. Serosal Decamethrin did not modify Na+ and H+ fluxes. In short circuit conditions, Decamethrin (10(-5) M) in the mucosal face inhibited the JnNa+; the JnH+ did not change in these conditions. The abscence of interaction of mucosal Decamethrin with Amiloride was shown.

A sea anemone toxin from Parasicyonis actinostoloides which inhibits the inactivation process of the sodium channel was acylated by using cold or tritium labeled propionyl N-hydroxysuccinimide ester. Acylation changed the isoelectric point of the peptide but did not change the toxicity to the crayfish nerve. Propionyl-toxin bound to leg nerves with Kd of 310 nM and Bmax of 104 pmol/g of wet nerve. The binding affinity and physiological activity of the toxin to crayfish nerves were suppressed with a common dependence on membrane depolarizations induced by elevated external K+ concentrations.

The fractionation of the liver of goldfish (Carassius auratus) was studied, and the properties of the microsomal fraction were examined. The microsomal fraction contained cytochrome P-450 and catalyzed the oxidation of aminopyrine, aniline, 7-ethoxycoumarin and benzo(a)pyrene. The oxidation activities were significantly lower than those of rat liver microsomes. The titration of cytochrome P-450 by potassium cyanide indicated the presence of multiple forms of cytochrome P-450 in goldfish liver microsomes. Feeding of goldfish with 3-methylcholanthrene-containing food greatly induced benzo(a)pyrene hydroxylation activity of the liver microsomes. The Soret peak of the carbon monoxide compound of cytochrome P-450 was shifted from 450 to 448 nm.

In the experiment of electrocardiogram, the crude venom of giant hornet (Vespa mandarinia) showed cardioactive effects on rat heart. The heart rate was accelerated within 5 min after injection of the venom intraperitoneally, then the heart beat was blocked, resulting in conduction delay. The cardioactive constituent was separated into two components by gel filtration. One which was high molecular species such as protein showed complete atrioventricular block. Another component, having a low molecular weight, was fractionated in 5 peaks, which accelerated heart rate.

On the two dopamine (DA)-sensitive giant neurones, PON (periodically oscillating neuron, excited by DA) and TAN (tonically autoactive neuron, inhibited by DA), of an African giant snail (Achatina fulica Férussac), effects of synthetic ergot derivatives, including lisuride and pergolide, which are considered to be dopamine agonists, were examined. Of the substances examined, three of the ergot derivatives related to pergolide, D-8,9-didehydro-6-propylergoline-8-methanol (LY149174), D-6-methyl-8 beta-(2-(methylsulfinyl)ethyl)ergoline (LY116470) and D-2-chloro-6-methyl-8 beta-(2-(methylsulfinyl)ethyl)ergoline (LY127817), showed excitatory effects on PON, while pergolide (D-8 beta-( (methylthio)methyl)-6-propylergoline, LY127809) and lisuride (N-D-6-methyl-8-isoergolenyl-N',N'-diethylcarbamide) had no effect. On the other hand, only D-6-methyl-8 beta-(2-(methylsulfinyl)ethyl)ergoline (LY116470) had any excitatory effects on TAN.