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M R Johnson

Publications and source records attributed to M R Johnson.

At least 289 records · Page 16Linked to original sources

The effect of cholera toxin and heat labile and heat stable Escherichia coli enterotoxin on cyclic AMP concentrations in small intestinal mucosa of pig and rabbit.

The effect of cholera toxin, heat labile and heat stable Escherichia coli enterotoxin on mucosal cyclic AMP concentrations was determined on the proximal jejunum of weanling pigs and young rabbits. Ligated loops were injected with solutions containing no enterotoxin for control and either cholera toxin, heat labile or heat stable E. coli enterotoxin. The loops were drained after either two, four or six hours incubation at which time accumulated fluid was recorded and mucosal samples removed for determination of cyclic AMP concentration. In the rabbit, cholera toxin and heat labile, but not heat stable E. coli enterotoxin stimulated intestinal secretion while in the pig all three enterotoxins induced net fluid accumulation. Cholera toxin and heat labile, but not heat stable E. coli enterotoxin elevated rabbit mucosal cyclic AMP concentrations. In the pig these enterotoxins had no significant effect on mucosal cyclic AMP concentrations. The results are inconsistent with the hypothesis that the adenyl cyclase system is an essential step for enterotoxin induced intestinal secretion. The activation of intestinal adenyl cyclase by bacterial enterotoxins may only be an associated and not a necessary event for the stimulation of intestinal secretion.

Animals↗

Effects of intraluminal glucose on intestinal secretion induced by heat stable and heat labile Escherichia coli enterotoxin, cholera toxin and theophylline.

Glucose, l-alanine, l-aspartate, l-methionine and glycine enhanced net fluid and electrolyte absorption in acute isolated loops of the proximal jejunum of weanling swine. The effect of glucose on intestinal secretion induced by heat stable and heat labile Escherichia coli entero-toxin, cholera toxin and theophylline was examined in both the proximal and distal jejunum of weanling swine. In the proximal jejunum glucose enhanced the rate of net fluid and electrolyte absorption. This increase was accompanied by an increase in unidirectional dosium absorption. In loops exposed to either heat stable or heat labile enterotoxins, glucose significantly decreased the rate of net fluid and electrolyte secretion. The magnitude of glucose enhancement in loops exposed to heat stable and heat labile enterotoxins was similar to adjacent control loops. However, glucose enhancement did not occur in loops exposed previously to cholera toxin or concurrently to theophylline. Therefore, cholera toxin and theophylline may inhibit substrate dependent sodium absorption in the proximal jejunum. In the distal jejunum glucose enhancement did occur but the rate of enhancement was less than in the proximal jejunum. In this region glucose enhancement was not evident in loops exposed to either theophylline, heat stable, heat labile or cholera toxin.

Amino Acids↗

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Costs and Cost Analysis↗

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Legislation, Drug↗

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Communication↗

Selective and potent analgetics derived from cannabinoids.

Based on the hypothesis that analgetic activity is a dissociable feature of the cannabinoid molecule, we examined modifications of the side chain, the phenolic moiety, and, most significantly, structures that lack the benzopyran functionality present in THC and (--)-9-nor-9 beta-hydroxyhexahydrocannabinol (HHC). A new grouping, the 1-methyl-4-phenylbutyloxy C-3 side chain, elaborates a unique lipopholic region. Replacement of the phenol substituent produced several derivatives which retain analgetic activity in the codeine potency range. Introduction of a weakly basic nitrogen at C-5 and deletion of the axial methyl group in the B ring, two structural changes forbidden by traditional cannabinoid SAR, resulted in a unique family of benzoquinolines with potent analgetic activity. The prototype of this series, levonantradol, exhibits potent and stereospecific analgetic and antiemetic activity.

Analgesics↗

Levonantradol: a role for central prostanoid mechanisms?

Although delta 9-tetrahydrocannabinol (THC) possesses many pharmacologic activities, attempts to define sites of biochemical action for the natural cannabinoids have been hampered by their low solubility, their low potency, and their relative lack of biologic selectivity. We have recently described a potent, cannabinoid-related analgetic, levonantradol, which acts stereospecifically in animals to produce analgesia qualitatively similar to morphine but at 1/9 to 1/34 the dose. While levonantradol does not act at or through the opiate receptor, the finding of one-way cross tolerance in animals suggests that morphine and levonantradol influence common nociceptive pathways. This report describes a striking structural homology between PGE1 and levonantradol as elucidated by x-ray and conformational studies. This observation is consistent with the generally recognized involvement of prostaglandins in pain and emesis and may have relevance to the site of levonantradol's analgetic actions. More importantly, it provides an ongoing, heuristic basis for exploring, in depth, the role of prostaglandins in the action of levonantradol and cannabinoids.

Animals↗