Richard P. Gregson

The occurrence of prostaglandins PGE2 and PGF2α in a plant - the red alga Gracilaria Lichenoides.

Abstract Prostaglandins PGE2 and PGF2α were isolated from the aqueous extract of the red alga Gracilaria lichenoides , after an investigation of the extracts anti-hypertensive properties.

Characterization of the neurotoxic constituents of Conus geographus (L) venom.

Abstract The crude venom of the marine gastropod Conus geographus (L) has been separated into three lethal constituents and their actions at the mammalian neuromuscular junction examined. Chromatography of the venom of Sephadex G-50 gave one toxic fraction, which was resolved by ion exchange chromatography on SP-Sephadex into three toxic components. These components were individually purified by diafiltration and Sephadex G-15 chromatography to give Toxins I,II and III. Toxins I and II in concentrations greater than 5 ug/ml reduced the amplitude of end-plate potentials and miniature end-plate potentials; Toxin I also blocked the depolarization of muscle fibres produced by carbachol; neither toxin affected the generation of action potentials in muscle fibres. Toxin III in concentrations greater than 5 ug/ml rapidly and reversibly blocked the generation of action potentials in muscle fibres; it had no effect on resting membrane potential nor on the amplitude of epps or mepps. It also slowly blocked the compound action potential recorded from isolated sciatic nerves but this was not reversible in the experiments. The rate at which this toxin blocked action potentials was increased by stimulation of the preparation. It is suggested that Toxin III acts by blocking the inward movement of sodium during activity. Toxin III appeared to be a nonadeca or eicosa peptide possibly having a cystine residue in the N-terminal position.

Isolation and synthesis of 1-methylisoguanosine, a potent pharmacologically active constituent from the marine sponge tenadia digitata

A new pharmacologically active agent isolated from the marine sponge Tedania digitata has been identified as 1-methylisoguanosine (1) by spectral and degradative chemical methods and synthesis from a β-D-ribofuranosylimidazole (2).

Stimulation of guinea-pig brain adenylate cyclase by adenosine analogues with potent pharmacological activity in vivo

Abstract 1-Methylisoguanosine, a marine natural product with potent muscle-relaxant and cardiovascular actions in vivo , interacts directly with adenosine receptors in guinea-pig brain slices to stimulate adenylate cyclase. These effects are blocked by theophylline. Comparison of the in vivo pharmacological activity of a number of synthetic analogues of 1-methylisoguanosine with in vitro adenylate cyclase-stimulating ability indicates that compounds lacking the latter biochemical activity have little muscle-relaxant activity. Adenosine is a potent stimulator of adenylate cyclase but is inactive in vivo because of rapid removal from the extracellular environment by uptake and deamination. Unlike adenosine, 1-methylisoguanosine is resistant to deamination and is only poorly accumulated by brain tissue slices or homogenates containing synaptosomes. Since it is an extremely weak competitive inhibitor of adenosine deaminase and only a weak inhibitor of adenosine uptake, it is unlikely to act by potentiating the effects of adenosine itself at extracellular receptors. Thus, the pharmacological effects of 1-methylisoguanosine are apparently due to its actions as a long-lasting adenosine analogue.

Isolation and characterization of a protein neurotoxin from the venom glands of the funnel-web spider (Atrax robustus)

1. Ground venom glands from male and female funnel-web spiders (Atrax robustus) were extracted with acetic acid (0.35 M). 2. A protein constituent of these extracts, atraxin, which caused muscle fasciculation when applied to the phrenic nerve-hemidiaphragm of the mouse in vitro, was isolated by the sequential application of ultrafiltration, gel permeation and ion exchange chromatography. 3. When subjected to isoelectricfocusing, amino acid analysis, ultracentrifugation, ultraviolet and 1H nuclear magnetic resonance spectroscopy, it was shown that atraxin had an approximate molecular weight of 9800, an isoelectric point of greater than 9 and that it contained 76 amino acid residues.

13 C n.m.r. spin–lattice relaxation time measurements determining the major tautomer of 1-methylisoguanosine in solution

Analysis of the contributions of 13C–1H dipolar interactions to the 13C n.m.r. spin-lattice relaxation times of the quaternary carbons of 1-methylisoguanosine establishes that the predominant tautomer in solution is the 2-keto, 6-amino form.

In vivo Actions of atraxin, a protein neurotoxin from the venom glands of the funnel-web spider (Atrax Robustus)

The effects of atraxin, a neurotoxic protein from the venom glands of the funnel-web spider (Atrax robustus), have been studied in anaesthetized monkeys. At doses of 70 and 80 micrograms kg-1 i.v., atraxin caused respiratory disturbances (dyspnoea and apnoea), and profound alterations in heart rate and blood pressure. These doses also caused salivation, lachrymation, skeletal muscle fasciculation and an elevation in body temperature. Concurrent increases in firing were recorded from the phrenic nerve and from respiratory and other skeletal muscles. It is concluded that atraxin produces the same syndrome in primates as that observed with whole milked male funnel-web venom.

Isolation of peptide hepatotoxins from the blue-green alga Microcystis aeruginosa

Abstract 1. A procedure has been developed for the isolation, quantitation and comparison of peptide hepatotoxins from the blue-green alga Microcystis aeruginosa. 2. The method is based on reverse phase HPLC coupled with a mouse lethality bioassay. 3. Analysis of an hepatotoxin, aeruginosin, by 1 H NMR spectroscopy revealed the presence of tyrosine, phenylalanine, methionine, an unsaturated moiety, leucine and/or isoleucine. 4. A toxic isolate from another M. aeruginosa bloom collected in the same region was shown to contain a toxin different to aeruginosin.

3-Hydroxy-4-methoxyphenethylamine, the cardioactive constituent of a soft coral

Intravenous administration to rats of the aqueous extract of the soft coralNephthea sp. caused an increase in heart rate and blood pressure. The cardioactive constituent was isolated and shown to be 3-hydroxy-4-methoxyphenethylamine.

The occurrence of 5-hydroxytryptamine in the holothurian,Pentacter crassa

5-Hydroxytryptamine (5-HT) and hypoxanthine were isolated chromatographically from the holothurianPentacter crassa. This study was initiated as a result of the observed hypotensive activity of aP. crassa extract. This activity was also encountered in extracts of the holothuriansThelenota ananus andStichopus chloronatus and can be attributed to 5-HT.