Melis M R, Stancampiano R, Argiolas A
Bernard B. Brodie Department of Neuroscience, University of Cagliari, Italy.
Naunyn Schmiedebergs Arch Pharmacol. 1995 Apr;351(4):439-45. doi: 10.1007/BF00169086.
The effect of the intracerebroventricular (i.c.v.) administration of NG-nitro-L-arginine methyl ester and NG-monomethyl-L-arginine, two inhibitors of nitric oxide (NO) synthase, on penile erection and yawning induced by 1-(3-chlorophenyl)-piperazine (m-CPP)- and N-(3-trifluoromethylphenyl)-piperazine (TFMPP), two selective 5HT1c receptor agonists, was studied in male rats. Both NO synthase inhibitors (50-500 micrograms i.c.v.) prevented dose-dependently the behavioural responses induced by m-CPP (0.5 mg/kg s.c.) or by TFMPP (1 mg/kg s.c.), but NG-nitro-L-arginine methyl ester was about 4-5 times more potent than NG-monomethyl-L-arginine. The D-isomer of NG-monomethyl-L-arginine, which does not inhibit nitric oxide synthase, was ineffective. The inhibitory effect of NG-nitro-L-arginine methyl ester on m-CPP- and TFMPP-induced responses was prevented by the administration of L-arginine (1 mg i.c.v.). In contrast, NG-nitro-L-arginine methyl ester (20 micrograms) was ineffective when injected in the paraventricular nucleus of the hypothalamus, a brain area that plays a key role in the expression of these behavioural responses. m-CPP- and TFMPP-induced penile erection and yawning was prevented also by the i.c.v. administration of LY 83583 (50-200 micrograms) or methylene blue (50-400 micrograms), two inhibitors of guanylate cyclase but not by reduced hemoglobin (50-400 micrograms), a NO scavenger. The results suggest that central nitric oxide is involved in the expression of penile erection and yawning induced by 5-HT1c receptor agonists.
研究了一氧化氮(NO)合酶的两种抑制剂——NG-硝基-L-精氨酸甲酯和NG-单甲基-L-精氨酸经脑室内(i.c.v.)给药对1-(3-氯苯基)-哌嗪(m-CPP)和N-(3-三氟甲基苯基)-哌嗪(TFMPP)这两种选择性5HT1c受体激动剂诱导的雄性大鼠阴茎勃起和打哈欠的影响。两种NO合酶抑制剂(脑室内注射50 - 500微克)均剂量依赖性地抑制m-CPP(皮下注射0.5毫克/千克)或TFMPP(皮下注射1毫克/千克)诱导的行为反应,但NG-硝基-L-精氨酸甲酯的效力比NG-单甲基-L-精氨酸强约4 - 5倍。不抑制一氧化氮合酶的NG-单甲基-L-精氨酸的D-异构体无效。脑室内注射L-精氨酸(1毫克)可消除NG-硝基-L-精氨酸甲酯对m-CPP和TFMPP诱导反应的抑制作用。相反,NG-硝基-L-精氨酸甲酯(20微克)注射到下丘脑室旁核(在这些行为反应的表达中起关键作用的脑区)时无效。脑室内注射鸟苷酸环化酶的两种抑制剂LY 83583(50 - 200微克)或亚甲蓝(五十 - 400微克)也可抑制m-CPP和TFMPP诱导的阴茎勃起和打哈欠,但一氧化氮清除剂还原血红蛋白(50 - 400微克)则无效。结果表明,中枢一氧化氮参与了5-HT1c受体激动剂诱导的阴茎勃起和打哈欠反应的表达。