Effect of Two Hemicholiniums on the Disposition and Distribution of Endogenous Free Choline in Anaesthetized Rabbits

Abstract

1 The effects of hemicholinium no. 3 (HC‐3) and its p‐terphenyl analogue (TPHC‐3) on the disposition and distribution of free choline were studied in rabbits under pentobarbitone anaesthesia. Free choline was determined by bioassay. 2 The respiration of animals given 0.35 μmol/kg of HC‐3 was hardly affected; however, 4 out of 6 rabbits given the same dose of TPHC‐3 exhibited varying degrees of respiratory impairment. All animals that received 2 injections (1 h apart) of either HC‐3 (1.4 μmol/kg) or TPHC‐3 (0.7 μmol/kg) developed respiratory difficulty about 1 h after the second injection. 3 The respiratory distress was accompanied by a 2 to 15‐fold rise in plasma choline concentration. This rise has been attributed to hypoxia. 4 In experiments in which choline has been infused it was observed that HC‐3 could impair the animal's ability to dispose of exogenous choline. In control rabbits neither HC‐3 nor TPHC‐3 produced changes in plasma choline concentrations unless the respiration was depressed. 5 Either HC‐3 or TPHC‐3 (both at 0.35 μmol/kg) significantly (P < 0.05) reduced the kidney choline concentration by 40% and 30% respectively; both hemicholiniums raised the lung choline concentration by about 35%. Only TPHC‐3 caused a significant rise (40%) in liver choline. The choline concentrations in other tissues were unaffected by the hemicholiniums.

UPTAKE OF 1:2-14C-CHOLINE BY THE GUINEA-PIG LUNG IN VITRO: AND THE EFFECTS OF P-TERPHENYL HEMICHOLINIUM-3

“…THPC-3 in this in vitro sytem, unlike that in the in vivo system of Gardiner & Gwee (1977), did not cause an increase of free chotine in the perfusion fluid, nor a significant increase in lung choline concentration at the end of an hour. The rise in plasma choline concentration observed in their in vivo experiments was due to hypoxia (Gardiner, 1975;Gardiner & Gwee, 1977) which did not exist in our in 'vitro system where the lung was artificially ventilated.…”

“…The rise in plasma choline concentration observed in their in vivo experiments was due to hypoxia (Gardiner, 1975;Gardiner & Gwee, 1977) which did not exist in our in 'vitro system where the lung was artificially ventilated. The ventilation could have also protected the lung from the breakdown of the uptakehelease mechanism(s) of choline.…”

“…The concentration of TPHC-3 used in this in vitro study was fixed at 30 nmol/ml to be comparable with those achieved in the in vivo study of Gardiner & Gwee (1977). They found that a total dose of 1.4 pmol/kg injected intravenously produced severe respiratory distress accompanied by statistically significant increase of plasma choline.…”

“…0305-1870/82/0200-0045 502.00 0 1982 Blackwell Scientific Publications transport into intracellular sites for acetylation thereby inhibiting acetylcholine synthesis; (reviewed by Bowman & Marshall, 1972). Gardiner & Gwee (1977) reported that during lethal intoxication HC-3 increased by 35% the endogenous concentration of choline in the lungs. They suggested that the increase in choline concentration could have been due to HC-3 inhibiting the incorporation of choline into surfactant lecithin.…”

“…The present communication reports the study of the in vilro perfusion of the guinea-pig lungs which was used to investigate the uptake of I4C-choline by the perfused lungs and the effects of p-terphenyl hemicholinium (TPHC-3), an analogue of HC-3 (Gardiner & Lee, 1969) on the perfused lung system. TPHC-3 resembling HC-3 in most of its actions has been found to be more potent (Gardiner & Lee, 1%9;Gardiner & Gwee, 1977).…”