Al-Kaleel Ali, Aygun Hatice, Al-Gailani Lubna, Kabak Yonca, Inal Sinem, Ayyildiz Mustafa, Him Aydin, Agar Erdal
Department of Physiology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey.
Faculty of Medicine, Cyprus International University, Nicosia, Cyprus.
Pflugers Arch. 2023 Jun;475(6):719-730. doi: 10.1007/s00424-023-02814-y. Epub 2023 Apr 27.
This study endeavoured to assess the effect of hemopressin (Hp), a nano peptide obtained from the alpha chain of hemoglobin, on chronic epileptic activity and its potential correlation with cannabinoid receptor type 1 (CB1). Male Wistar albino rats (230-260 g) were used. The kindling process was conducted by administering a sub-convulsant dose of pentylenetetrazol (PTZ) (35 mg/kg, i.p) three times a week for a maximum of 10 weeks. Tripolar electrodes and external cannula guides for intracerebroventricular (i.c.v) injections were surgically implanted in the skulls of kindled rats. On the day of the experiment, doses of Hp, AM-251, and ACEA were administered prior to the PTZ injections. Electroencephalography recordings and behavioural observations were conducted simultaneously for 30 min after the PTZ injection. The administration of Hp (0.6 μg, i.c.v) resulted in a decrease in epileptic activity. The CB1 receptor agonist ACEA (7.5 μg, i.c.v) showed an anticonvulsant effect, but the CB1 receptor antagonist AM-251 (0.5 μg, i.c.v) displayed a proconvulsant effect. The co-administration of Hp (0.6 μg, i.c.v) and ACEA (7.5 μg, i.c.v) and of Hp (0.6 μg, i.c.v) and AM-251 (0.5 μg, i.c.v) produced an anticonvulsant effect. However, when AM-251 was administered prior to Hp, it produced a proconvulsant impact that overrode Hp's intended anticonvulsant effect. Interestingly, the co-administration of Hp (0.03 μg) + AM-251 (0.125 μg) unexpectedly exhibited an anticonvulsant effect. Electrophysiological and behavioural evaluations demonstrated the anticonvulsant effect of Hp in the present model, highlighting the possibility that Hp may act as an agonist for the CB1 receptor.
本研究旨在评估从血红蛋白α链获得的纳米肽血加压素(Hp)对慢性癫痫活动的影响及其与1型大麻素受体(CB1)的潜在相关性。使用雄性Wistar白化大鼠(230 - 260克)。通过每周三次给予亚惊厥剂量的戊四氮(PTZ)(35毫克/千克,腹腔注射)进行点燃过程,最长持续10周。将用于脑室内(i.c.v)注射的三极电极和外部套管引导器手术植入点燃大鼠的颅骨中。在实验当天,在注射PTZ之前给予Hp、AM - 251和ACEA的剂量。在注射PTZ后同时进行30分钟的脑电图记录和行为观察。给予Hp(0.6微克,脑室内注射)导致癫痫活动减少。CB1受体激动剂ACEA(7.5微克,脑室内注射)显示出抗惊厥作用,但CB1受体拮抗剂AM - 251(0.5微克,脑室内注射)表现出促惊厥作用。联合给予Hp(0.6微克,脑室内注射)和ACEA(7.5微克,脑室内注射)以及Hp(0.6微克,脑室内注射)和AM - 251(0.5微克,脑室内注射)产生了抗惊厥作用。然而,当在Hp之前给予AM - 251时,它产生了促惊厥作用,超过了Hp预期的抗惊厥作用。有趣的是,联合给予Hp(0.03微克)+ AM - 251(0.125微克)意外地表现出抗惊厥作用。电生理和行为评估证明了Hp在本模型中的抗惊厥作用,突出了Hp可能作为CB1受体激动剂的可能性。