Biomedical subjects
Publications and source records attributed to H Edery.
The cat isolated jejunum kept either in an organ-bath or under superfusion can be rendered extremely sensitive to bradykinin after exposure to chymotrypsin. Treated preparations responded to as little as 100 pg/ml of the peptide. Use has been made of sensitized preparations to determine bradykinin-like material of dog blood extracts obtained in experimental "dumping syndrome".
Repeated, but not single, intraperitoneal injections of delta1,6-tetrahydrocannabinol (delta1,6-THC) 20 mg/kg to rats administered daily for two weeks, produced increased gamma-aminobutyric acid (GABA) concentration and decreased glutamic acid decarboxylase (GAD) activity in the cerebellum, as well as enhancement of [3H]-GABA uptake by cerebellar crude synaptosomes. It seems that the motor impairment elicited by delta1,6-THC was not associated with the GABA system, but presumably might be related to changes in brain excitability.
1 Cats were anaesthetized with pentobarbitone sodium and atropinized peripherally by intravenous injection of atropine methyl nitrate; the effect was examined of topical bilateral application of dyflos to the ventral surface of the medulla oblongata at a region lateral to the pyramids and caudal to the trapezoid bodies. Dyflos was applied by means of perspex rings; the volume of fluid placed in each ring was 10 mul.2 The topical application of dyflos (1-20 mg/ml) produced a fall in arterial blood pressure without changes in heart rate and, in experiments without artificial ventilation, tachypnoea with dissociation of thoracic and abdominal respiration.3 Atropine methyl nitrate (50 mg/ml) applied topically in the same way as dyflos, prevented or abolished its vasodepressor effect.4 The two reactivators of acetylcholinesterase, obidoxime (100-200 mg/ml) and pralidoxime mesylate (100-200 mg/ml), applied topically in the same way as dyflos, abolished its vasodepressor effect. The reactivator compound 30 (100 mg/ml), also a pyridinium aldoxime, did not have this effect.5 Obidoxime and pralidoxime mesylate also reversed the vasodepression produced by carbachol applied to the ventral surface of the brain stem but not the vasodepression produced by glycine similarly applied.6 The problem is discussed as to whether the reversal of the dyflos and carbachol-induced vasodepression by obidoxime and pralidoxime is due to acetylcholinesterase reactivation by dephosphorylation and decarbamylation respectively, to a central atropine-like action of these compounds or to a combination of both.
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6beta-Hydroxy-delta(1)-tetrahydrocannabinol, a metabolite of delta(1)-tetrahydrocannabinol has been synthesized from delta(6)-tetrahydrocannabinol. It shows high tetrahydrocannabinol-type activity in rhesus monkeys. The implications of this funding are discussed.
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A sample of hashish was extracted consecutively with petroleum ether, benzene, and methanol. When tested intravenously in monkeys only the petroleum-ether fraction was active. This material was further fractionated. The only active compound isolated was Delta(1)-tetrahydrocannabinol. Cannabinol, cannabidiol, cannabichromene, cannabigerol, and cannabicyclol when administered together with Delta(1)-tetrahydrocannabinol do not cause a change in the activity of the latter, under the experimental conditions used. These results provide evidence that, except for Delta(1)-tetrahydrocannabinol, no other major, psychotomimetically active compounds are present in hashish.
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1. The influence of various materials, principally hydrolases and peptides, on the sensitivity to stimulating substances has been studied in a wide range of isolated and in vivo smooth muscle preparations.2. Chymotrypsin raised the susceptibility of the guinea-pig isolated ileum to peptides related to bradykinin and also sensitized isolated ileum and fundus of rat and albino gerbil to bradykinin. No sensitization to the kinin occurred in the following preparations: rat, gerbil and rabbit duodenum; rat colon and urinary bladder; dog tracheal chain; and rabbit jejunum. Chymotrypsin and peptides structurally related to the active centre of the enzyme did not affect the permeability increasing property of bradykinin in guinea-pig skin micro-circulation vessels. In contrast, intravenously administered chymotrypsin markedly augmented the bronchoconstrictor action of the kinin.3. Ficin and pronase increased the sensitivity of guinea-pig ileum to bradykinin. Pronase also sensitized the gerbil ileum and this effect was abolished by previous treatment with di-isopropylfluorophosphonate (dyflos). Pronase destroyed bradykinin after incubation.4. Reduced glutathione potentiated the response to bradykinin of guinea-pig ileum but did not affect its sensitivity. The potentiation also occurred in a chymotrypsin-treated preparation.5. It is assumed that specific sensitization elicited by proteinases might derive from an effect on the protein envelope of smooth muscle membrane.
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