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Glucose and cation transport in rat jejunum, ileum and colon in vivo: control experiments, and effect of cationic surfactant.

Osmotically balanced solutions of glucose (0.5-300 mM) and sodium chloride, containing cetrimonium bromide (cetrimide, 0.8-4.1 mM), were instilled into the jejunum, ileum and colon of anaesthetized rats. Net transport of glucose, sodium and potassium was studied by their disappearance from, or accumulation into the intestinal lumen during 15 min incubation. Cetrimide caused the following shifts in normal jejunal and ileal glucose absorption: At low luminal glucose levels, absorption was strongly depressed and may be converted to net secretion. At intermediate levels, inhibition was less pronounced, and at high luminal glucose levels absorption was enhanced. Similar changes were seen in the colon. Furthermore, cetrimide caused a three-fold change in the regression lines relating net sodium fluxes to the initial sodium concentration: The lines became steeper, the correlation was improved and the sodium concentration value corresponding to zero net transport was elevated. Net potassium secretion was increased. These changes are all consistent with the view that surfactants cause an increase in passive permeability. Quantitatively, the effect of cetrimide increased with localization in the order colon greater than ileum greater than jejunum. Benzalkonium chloride (0.5-1.7 mM) was tested in the ileum only, and caused quite similar effects.

Animals↗

Effects of divalent cations, cation chelators and an ionophore on morphine analgesia and tolerance.

The analgesic effect of morphine was antagonized in mice by intracerebroventricular injection of Ca++, Mg++ and Mn++ and was potentiated by ethylene glycol tetraacetic acid but was not altered by Sr++, Ba++, Ni++, Hg++, Cd++ or ethylenediamine tetraacetic acid. The antagonistic effect of Ca++ was not altered by pretreatment with pargyline or 6-hydroxydopamine indicating that altered release of catecholamines or serotonin was not involved in this action of Ca++. Induction of morphine tolerance by pellet implantation also did not alter the antagonistic effect of Ca++. The antagonistic effects of Ca++ and naloxone were additive in both nontolerant and tolerant animals and the apparent affinity of naloxone for its receptors, as estimated by in vivo pA2 determinations, was not altered by Ca++. However, the ionophore X537A was found to increase greatly the narcotic antagonist effect of a low dose of Ca++ although the ionophore alone did not alter the effects of morphine. This indicates that Ca"++ must penetrate cell membranes in order to reduce the analgesic effects of morphine. These findings indicate the importance of Ca++ localization in the actions of narcotic agonists and antagonists.

Analgesia↗

Effects of divalent cations, lanthanum, cation chelators and an ionophore on acetylcholine antinociception.

The antinociceptive effect of intracerebroventricularly administered acetylcholine as measured in the mouse tail-flick test was reduced by intracerebroventricularly injected calcium, magnesium and manganese. Maximum antagonism of acetylcholine-induced antinociception was observed with a 1-hour calcium pretreatment. Significant reduction existed at 2- but not 4-hour pretreatment. Barium and strontium were inactive. The antinociceptive effect of acetylcholine was potentiated by lanthanum and ethylene glycol tetraacetic acid but not by ethylenediamine tetraacetic acid. The ionophore A23187 was shown to increase greatly the antagonistic effect of a low dose of calcium. The ionophore alone did not significantly alter the effect of acetylcholine. Thus, it appears that calcium must penetrate cell membranes to reduce the effect of acetylcholine. In addition to acetylcholine, it was found that the antinociceptive effects of oxotremorine and physostigmine could also be reduced by calcium. These data indicate that alterations in intracellular calcium are involved in cholinergically induced antinociception.

Acetylcholine↗