Takeshi Honma

Effects of short-term toluene exposure on ligand binding to muscarinic acetylcholine receptors in the rat frontal cortex and hippocampus.

Changes in the binding affinity of the muscarinic acetylcholine receptor agonist carbamylcholine were determined in membranes isolated from the brains of rats exposed to toluene at concentrations of 500-2,000 ppm for 6 h. Membrane fractions of the frontal cortex and hippocampus were prepared and agonist-binding affinities were determined by measuring the displacement of [3H]N-methyl scopolamine-binding activity by carbamylcholine. In the frontal cortex, the affinity of high-affinity carbamylcholine binding was reduced following exposure to toluene at a concentration of 1000 ppm or higher. However, in the hippocampus, the affinity of high-affinity binding of carbamylcholine was increased following exposure to toluene. These observations suggest that toluene exposure affects binding affinity of carbamylcholine, and the effect differs by brain region.

Inhalation of 1-Bromopropane Causes Excitation in the Central Nervous System of Male F344 Rats

The present study investigates the effects of 1-bromopropane (1BP) on animal behavior to determine the extent of toxicity to the central nervous system (CNS). We measured the spontaneous locomotor activity (SLA) of rats before and after 3 weeks of exposure to 1BP for 8 h per day. In control and 10 ppm groups, the SLA values were similar to pre-exposure levels on post-exposure Day 1 and thereafter. However, the SLA values in the 50 and 200 ppm groups were higher than pre-exposure levels. Open-field behavior was evaluated after exposure and freezing time decreased with exposure to increasing concentrations of 1BP. Ambulation and rearing scores in the exposed groups were higher than control values, particularly in the 50 and 200 ppm groups. The frequency of defecation and urination decreased almost dose-dependently. Exposure to 50-1000 ppm of 1BP did not affect passive avoidance behavior examined using a step-through type apparatus. The amount of time swimming in the water maze test was not affected in the controls, or groups exposed to 50 and 200 ppm 1BP, but that in the 1000 ppm group was increased compared with control. Exposure at 50-1000 ppm dose-dependently decreased the traction performance of rats, indicating decreased muscle strength. We found that 10-200 ppm of 1BP exposure did not affect motor coordination determined by rota-rod performance. The increased SLA values and open-field activity support the notion that 1BP has excitatory effects on the CNS of F344 male rats. In addition, 1BP reduced the grip or muscle strength of the rats. Memory function was not disordered and the motor coordination of all four limbs remained normal.

Influence of 2-bromopropane on reproductive system--short-term administration of 2-bromopropane inhibits ovulation in F344 rats.

The present study was performed to investigate the toxic effects of 2-bromopropane (2BP) on the female reproductive system. Female F344 rats were administered 2BP (500 or 1000 mg/kg, i.p.) at intervals of 2 or 3 days for 15-17 days. The body weights were measured and estrous stages were observed throughout the experimental period. Ovulation, organ weights, ovarian histology, and blood biochemistry were investigated on the terminal day of the experiment. Uterine weights in rats treated with 2BP were significantly lower than those in control animals. Body, liver, kidney, and adrenal weights in 2BP-treated rats showed no significant differences from control values. 2BP treatment prolonged estrous cycles and decreased the number of ovulated ova in spontaneous ovulation. In addition, histological examinations showed that the preovulatory follicles in the ovary were altered markedly in 2BP groups. These results show that even in short-term treatment, 2BP injured the ovary, particularly the preovulatory follicles. It appears that these damages of the preovulatory follicles induced by 2BP reduced the numbers of spontaneously ovulated ova in female F344 rats.

Effects of toluene on regulation of adenylyl cyclase by stimulation of G-protein-coupled receptors expressed in CHO cells.

We determined the effects of toluene exposure on activation or inhibition of adenylyl cyclase by stimulating human beta2-adrenergic receptors (beta2-AR) and muscarinic acetylcholine receptor (mAChR) m2 subtypes, respectively, expressed in CHO cells. The formation of cAMP via beta2-AR stimulation was slightly but not significantly facilitated in the presence of 3.7 microM toluene. On the other hand, the inhibition of adenylyl cyclase by 10 microM of carbamylcholine stimulation of mAChR m2 subtypes was attenuated in the presence of toluene. These results strongly suggest that toluene affects activation of Gi rather than Gs.