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AIM: To explore the modulation of 2-arachidonoylglycerol (2-AG) on A-type potassium channels injured by kainic acid (KA) and its molecular mechanism. METHODS: Primary cultured caudate nucleus (CN) neurons were treated with KA to establish a neuroexcitatory toxicity model. Whole-cell patch clamp recording was performed to observe the changes of electrical activity of A-type potassium channels induced by KA-induced excitatory toxicity and 2-AG-mediated neuroprotective effect. RESULTS: In cultured CN neurons, patch clamp experiments confirmed that KA significantly decreased the A-type potassium channel current (Iʌ) density and changed the electrical function of CN neurons: the slope (k) of inactivation curve and the recovery time constant (τ) after inactivation of A-type potassium channels in CN neurons were significantly increased. The experiments showed that the increase in 2-AG level, whether using 2-AG directly or application of monoacylglycerol lipase inhibitor URB602 to decrease 2-AG metabolism and increase 2-AG level indirectly, inhibited the KA-induced reduction of Iʌ density and the changes of electrical activity of A-type potassium channels through cannabinoid receptor 1 (CB1R) : 2-AG effectively antagonized the KA-induced increases in τ value and k value for inactivation of A-type potassium channels, which accelerated the recovery process after inactivation of the channels. CONCLUSION: The changes of the electrical characteristics of A-type potassium channels may be one of the mechanisms of KA-induced excitotoxic injury of CN neurons. The 2-AG plays a neuroprotective role in KA-induced neuroexcitatory toxic model by regulating the function of A-type potassium channels through CB1R. [ABSTRACT FROM AUTHOR]

Objective To explore the expression pattern of cannabinoid receptor 1 (CBR1) in reproductive toxicity induced by dibutyl phthalate (DBP) exposure in male rats, and investigate the underlying mechanism. Methods Sixty healthy male Sprague-Dawley rats were randomly divided into 4 groups (15 animals in each group), that is, control group, and low-, medium- and high-dose groups, exposure to 100, 250 and 500 mg/kg DBP, respectively, by intragastric injection daily for 28 consecutive days. Computer-aided sperm analysis system (CASA) was used to detect sperm vitality, concentration, and rate of deformity. HE staining was employed to observe the changes in testicular tissue. The serum levels of testosterone (T), estradiol (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH) and sex hormone binding protein (SHBG) were measured by ELISA. The expression of p38, ERK, AKT and CBR1 at mRNA and protein levels was measured by RT-PCR and Western blotting. Results Compared with the control rats, the sperm motility and total sperm motility were reduced in low- (20.1±9.2 and 73.6±3.2), middle- (22.3±6.2 and 40.7±24.4) and high-dose (21.0±14.2 and 41.2±4.6) exposure groups (P < 0.05). Sperm concentration was significantly lower in the high-dose group (152.0±67.0, P < 0.05). Compared with the control group, serum T levels were significantly lower in the middle- (19.65±2.65) and high-dose groups (17.40±3.50, both P < 0.05). The serum level of E2 was significantly decreased in each exposure group (2.09±0.08, 2.11±0.77, 2.05±0.02) when compared to the control group. So were the serum LH levels (7.80±1.42, 7.68±2.28, 6.43±0.90) (all P < 0.05). While the serum level of FSH was all significantly increased in each exposure group (2.88±0.37, 2.89±0.29, 3.37±0.30), when compared to the control group (P < 0.05). In the testis tissue, the expression of CBR1 was increased at mRNA and protein levels than that of the control group, and the expression of p-p38 and p-ERK was significantly decreased than the control group (P < 0.05). Conclusion DBP exposure results in impairment of testicular tissue structure and decrease of sperm motility in male rats, which may be due to the up-regulation of CBR1 and the subsequent inhibition of ERK/p38MAPK phosphorylation.