Frederick A. Fuhrman

The occurrence of tetrodotoxin (tarichatoxin) in amphibia and the distribution of the toxin in the organs of newts (Taricha)

Abstract Among amphibia tetrodotoxin was found by bioassay only in the family Salamandridae. It was present in substantial concentration (mean value of about 25 μg per g) only in the genus Taricha: T. torosa, T. rivularis, T. granulosa; smaller amounts (1–4 μg per g) were found in Notophthalmus viridescens, Cynops pyrrhogaster, C. ensicauda and trace amounts (less than 0·1 μg per g) in Triturus vulgaris, T. cristatus, T. alpestris, T. marmoratus. This toxin was not detected in fourteen species of the orders Caudata and Salientia. In adult Taricha torosa, tetrodotoxin is concentrated in the skin, ovaries and ova, muscle and blood and is present in trace amounts in the liver, viscera and testes

Differentiation of the actions of tetrodotoxin and saxitoxin

Abstract While tetrodotoxin and saxitoxin are very similar in their actions, they can be differentiated biologically by the observation that newts of the genus Taricha are resistant to tetrodotoxin but not to saxitoxin. The resistance of these newts is due to a remarkable insensitivity of the somatic motor nerves to tetrodotoxin. The isolated desheathed sciatic nerve of Taricha torosa is at least 30,000 times more resistant than frog nerve. As seen in electronmicroscopic sections, there is no special enveloping structure around taricha nerves that can be considered as a particularly effective diffusion barrier. The isolated, desheathed brachial nerve of the Atlantic puffer fish, Spheroides maculatus , is about 1000 times more resistant to tetrodotoxin than frog nerve. Both taricha and tetrodon nerves are readily blocked by saxitoxin. Both nerves require external sodium ions for activity since replacement of Na + with choline, tris (hydroxymethyl) aminomethane or dimethyl-diethanol ammonium ion reduced the spike amplitudes. The resistance of these nerves to tetrodotoxin is interpreted as being a result of peculiarities in membrane structures that prevent an effective association with tetrodotoxin.

Identity of Tarichatoxin and Tetrodotoxin

Tarichatoxin (C11H17N3O8), a potent neurotoxin recently isolated in pure form from the eggs of the California newt, Taricha torosa, has been found to be identical to tetrodotoxin from the ovaries of Sphoeroides rubripes, the Japanese Fugu or puffer fish. As yet this substance has been detected only in a single family of fish, Tetraodontidae, and in a single family of amphibia, Salamandridae.

Toxin from Skin of Frogs of the Genus Atelopus: Differentiation from Dendrobatid Toxins

A potent, dialyzable toxin (atelopidtoxin) occurs in the skin of frogs of the genus Atelopus. A concentrate of atelopidtoxin from Atelopus zeteki has an LD50 in mice of 16 micrograms per kilogram. It differs from batrachotoxin, tetrodotoxin, and saxitoxin, the only known nonprotein substances of greater toxicity, as well as from all toxins previously isolated from amphibia.

Chemistry and pharmacology of skin toxins from the frog Atelopus zeteki (atelopidtoxin: zetekitoxin).

Abstract Chemistry and pharmacology of skin toxins from the frog Atelopus zeteki (atelopidtoxin; zetekitoxin). Toxicon 15, 115–128, 1977.—Zetekitoxins were obtained in purified form from skins of the Panamanian frog Atelopus zeteki by a series of steps which used preparative free-flowing electrophoresis in the last stages. The minor, less toxic component (zetekitoxin C) had an ld 50 of 80 μg per kg (i.p., mouse), and the major, more toxic component (zetekitoxin AB) had an ld 50 of 11 μg per kg. These toxins are water-soluble, low molecular weight, non-polypeptide, non-steroid and non-carbohydrate in nature. The zetekitoxins are clearly different from tetrodotoxin and chiriquitoxin. Atelopus zeteki were resistant to toxin obtained from their own skins. Zetekitoxin AB (1·5–3 μg per kg) produced sustained hypotension in anesthetized dogs and cats, during which time the pressor response to epinephrine and norepinephrine was unchanged, but that to carotid occlusion was reduced. The toxin at a concentration of 0·5 μg per 1 blocked vasoconstriction caused by electrical stimulation of perfused rabbit ear arteries, and this effect was antagonized by dextroamphetamine. It did not reduce contraction of the nicitating membrane or block α-adrenergic receptors (vas deferens). It partially blocked β-adrenergic receptors (guinea pig atria) only in high concentrations above 10 μg per 1.

EVIDENCE OF INJURY TO TISSUES AFTER HYPERTHERMIA.

Two criteria of injury by heat were used to ascertain whether hyperthermia produced changes that were detectable in tissues subsequently removed from the animals and incubated at 43 C. These criter...

Atelopidtoxin from the Panamanian frog, Atelopus zeteki☆

Abstract A water soluble, dialyzable toxin from the skin of the Panamanian frog, Atelopus zeteki , has been partially purified by a combination of dialysis, gel filtration, cellulose column chromatography and precipitation from water with acetone. This toxin, designated atelopidtoxin, at its present state of purity has a ld 50 (i.p., mice) of about 0·016 mg per kg, and thus has a toxicity which is only slightly less than the most lethal non-protein toxins known. When injected into mammals it produces hypotension and ventricular fibrillation. Its chemical and pharmacological properties exclude the possibility that it is batrachotoxin, isobatrachotoxin, tetrodotoxin or saxitoxin, the only known non-protein toxins which are more lethal than atelopidtoxin.

The Bushman arrow toxin, diamphidia toxin: Isolation from pupae of Diamphidia nigro-ornata

The Bushmen of the Kalahari Desert in Botswana use the pupae of the beetle Diamphidia nigro-ornata Ståhl to poison their arrows. Sequential aqueous extraction, ammonium sulfate precipitation, ultrafiltration and chromatofocusing have given an apparently homogeneous active protein from these pupae with an approximate mol. wt of 54,000, an isoelectric point of about 8.0 pH and a lethal potency (minimum lethal dose, MLD) between 5 and 20 micrograms/kg (i.p. mouse). Preliminary pharmacological studies on less purified material show that, after a delay, this Diamphidia toxin causes sustained contraction of isolated intestinal smooth muscle. This contraction is not blocked by atropine or mepyramine and, therefore, is not due to release of acetylcholine or histamine. Results on the phrenic nerve - hemidiaphragm preparation demonstrate that in the presence of the toxin, contraction in response to indirect stimulation gradually fails and is accompanied by contracture. Since direct stimulation of the muscle still elicits a contraction, the toxin apparently does not affect the contractile mechanism itself. We conclude that Diamphidia pupae contain a protein toxin that is responsible for its lethality. Although this toxin appears to differ in some properties from the toxins reported by Mebs et al., de la Harpe et al. and Kündig, these protein preparations undoubtedly correspond to each other. We did not find any evidence of the low molecular weight toxic component reported by Mebs et al.

Choline esters in the marine gastropods Nucella emarginata and Acanthina spirata: A new choline ester, tentatively identified as N-methylmurexine

Abstract 1. Several tissues of two intertidal gastropod mollusks belonging to the superfamily Muricacea contained, in addition to acetylcholine, other choline esters that produced contraction of the frog rectus abdominis muscle. 2. One major active choline ester found in acetone extracts of the hypobranchial gland of Acanthina spirata had pharmacological properties and a nuclear magnetic resonance spectrum consistent with murexine [urocanylcholine, β -[4-imidazolyl]acrylcholine). 3. A principal active compound from the hypobranchial gland of Nucella ( = Thais ) emarginata differed pharmacologically from murexine and was tentatively identified by nuclear magnetic resonance spectroscopy as the previously unreported N -methyl derivative of murexine, β -[4-(1-or 3-methyl)-imidazolyl]acrylcholine.

Inhibition of Brain Respiration by Ethyl Alcohol at Varied Temperature Levels

Summary The inhibition of oxygen consumption of rat cerebral cortex slices by ethyl alcohol was studied at 37.7 C, 30 C and 20 C. The inhibition becomes progressively greater with time at 37.7 C; such progressive inhibition is less marked at 30 C and is absent at 20 C. The minimum effective inhibitory concentration increases with decrease in temperature. The percentage inhibition with a given concentration of alcohol decreases with decrease in temperature.