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Pentadecapeptide BPC 157 counteracts L-NAME-induced catalepsy. BPC 157, L-NAME, L-arginine, NO-relation, in the suited rat acute and chronic models resembling 'positive-like' symptoms of schizophrenia.
Behavioural Brain Research ( IF 2.7 ) Pub Date : 2020-09-18 , DOI: 10.1016/j.bbr.2020.112919
Andrea Zemba Cilic 1 , Mladen Zemba 1 , Matija Cilic 1 , Igor Balenovic 1 , Sanja Strbe 1 , Spomenko Ilic 1 , Jaksa Vukojevic 1 , Zoran Zoricic 1 , Igor Filipcic 1 , Antonio Kokot 1 , Domagoj Drmic 1 , Alenka Boban Blagaic 1 , Ante Tvrdeic 1 , Sven Seiwerth 1 , Predrag Sikiric 1
Affiliation  

In the suited rat-models, we focused on the stable pentadecapeptide BPC 157, L-NAME, NOS-inhibitor, and L-arginine, NOS-substrate, relation, the effect on schizophrenia-like symptoms. Medication (mg/kg intraperitoneally) was L-NAME (5), L-arginine (100), BPC 157 (0.01), given alone and/or together, at 5 min before the challenge for the acutely disturbed motor activity (dopamine-indirect/direct agonists (amphetamine (3.0), apomorphine (2.5)), NMDA-receptor non-competitive antagonist (MK-801 (0.2)), or catalepsy, (dopamine-receptor antagonist haloperidol (2.0)). Alternatively, BPC 157 10 μg/kg was given immediately after L-NAME 40 mg/kg intraperitoneally. To induce or prevent sensitization, we used chronic methamphetamine administration, alternating 3 days during the first 3 weeks, and challenge after next 4 weeks, and described medication (L-NAME, L-arginine, BPC 157) at 5 min before the methamphetamine at the second and third week. Given alone, BPC 157 or L-arginine counteracted the amphetamine-, apomorphine-, and MK-801-induced effect, haloperidol-induced catalepsy and chronic methamphetamine-induced sensitization. L-NAME did not affect the apomorphine-, and MK-801-induced effects, haloperidol-induced catalepsy and chronic methamphetamine-induced sensitization, but counteracted the acute amphetamine-induced effect. In combinations (L-NAME + L-arginine), as NO-specific counteraction, L-NAME counteracts L-arginine-induced counteractions in the apomorphine-, MK-801-, haloperidol- and methamphetamine-rats, but not in amphetamine-rats. Unlike L-arginine, BPC 157 maintains its counteracting effect in the presence of the NOS-blockade (L-NAME + BPC 157) or NO-system-over-stimulation (L-arginine + BPC 157). Illustrating the BPC 157-L-arginine relationships, BPC 157 restored the antagonization (L-NAME + L-arginine + BPC 157) when it had been abolished by the co-administration of L-NAME with L-arginine (L-NAME + L-arginine). Finally, BPC 157 directly inhibits the L-NAME high dose-induced catalepsy. Further studies would determine precise BPC 157/dopamine/glutamate/NO-system relationships and clinical application.



中文翻译:

Pentadecapeptide BPC 157 可抵消 L-NAME 引起的僵住症。BPC 157、L-NAME、L-精氨酸、NO 相关性,在适合的大鼠急性和慢性模型中,类似于精神分裂症的“阳性样”症状。

在合适的大鼠模型中,我们专注于稳定的十五肽 BPC 157、L-NAME、NOS 抑制剂和 L-精氨酸、NOS 底物关系,以及对精神分裂症样症状的影响。药物(mg/kg 腹腔注射)是 L-NAME (5)、L-精氨酸 (100)、BPC 157 (0.01),单独和/或一起给药,在攻击急性紊乱的运动活动(多巴胺-间接/直接激动剂(苯丙胺 (3.0)、阿扑吗啡 (2.5))、NMDA 受体非竞争性拮抗剂(MK-801 (0.2))或僵住症(多巴胺受体拮抗剂氟哌啶醇 (2.0))。或者,BPC 157腹腔注射 L-NAME 40 mg/kg 后立即给予 10 μg/kg。为了诱导或预防致敏,我们使用慢性甲基苯丙胺给药,在前 3 周交替 3 天,在接下来的 4 周后进行攻击,并描述药物(L -姓名,L-精氨酸,BPC 157)在第二周和第三周甲基苯丙胺前 5 分钟。单独服用 BPC 157 或 L-精氨酸可抵消苯丙胺、阿扑吗啡和 MK-801 诱导的作用、氟哌啶醇诱导的强直性昏厥和慢性甲基苯丙胺诱导的致敏作用。L-NAME 不影响阿扑吗啡和 MK-801 诱导的作用、氟哌啶醇诱导的僵住症和慢性甲基苯丙胺诱导的致敏作用,但抵消了急性苯丙胺诱导的作用。在组合 (L-NAME + L-精氨酸) 中,作为 NO 特异性对抗作用,L-NAME 在阿扑吗啡-、MK-801-、氟哌啶醇-和甲基苯丙胺-大鼠中抵消 L-精氨酸诱导的对抗作用,但在苯丙胺-大鼠中无效老鼠。与 L-精氨酸不同,BPC 157 在 NOS 阻断(L-NAME + BPC 157)或 NO 系统过度刺激(L-精氨酸 + BPC 157)存在时保持其抵消作用。说明 BPC 157-L-精氨酸关系,BPC 157 恢复了拮抗作用(L-NAME + L-精氨酸 + BPC 157),当它被 L-NAME 与 L-精氨酸(L-NAME + L-精氨酸)。最后,BPC 157 直接抑制 L-NAME 高剂量诱导的僵住症。进一步的研究将确定精确的 BPC 157/多巴胺/谷氨酸/NO 系统关系和临床应用。BPC 157 直接抑制 L-NAME 高剂量诱导的僵住症。进一步的研究将确定精确的 BPC 157/多巴胺/谷氨酸/NO 系统关系和临床应用。BPC 157 直接抑制 L-NAME 高剂量诱导的僵住症。进一步的研究将确定精确的 BPC 157/多巴胺/谷氨酸/NO 系统关系和临床应用。

更新日期:2020-09-26
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