B2-kinin receptors in the dorsal periaqueductal gray are implicated in the panicolytic-like effect of opiorphin

作者：Sestile Caio Cesar^*; Maraschin Jhonatan Christian; Rangel Marcel Pereira; Santana Rosangela Getirana; Zangrossi Helio Jr; Graeff Frederico Guilherme; Audi Elisabeth Aparecida^*

来源：Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2017, 79: 493-498.

DOI：10.1016/j.pnpbp.2017.08.003

• Opiorphin
• Bradykinin
• Panic model
• 5-HT1A receptor
• Kinin B2 receptor

Reported results have shown that the pentapeptide opiorphin inhibits oligopeptidases that degrade brain neuropeptides, and has analgesic and antidepressant effects in experimental animals, without either tolerance or dependency after chronic administration. In a previous study we showed that opiorphin has a panicolytic-like effect in the dorsal periaqueductal gray (dPAG) electrical stimulation test (EST), mediated by the mu-opioid receptor (MOR). This study further analyzes the mechanism of opiorphin panicolytic action, using the EST and drug injection inside the dPAG. The obtained results showed that blockade of the 5-HT1A receptors with WAY-100635 did not change the escape-impairing effect of opiorphin, and combined injection of sub-effective doses of opiorphin and the 5-HT1A-agonist 8-OH-DPAT did not have a significant anti-escape effect. In contrast, the anti-escape effect of opiorphin was antagonized by pretreatment with the kinin B2 receptor blocker HOE-140, and association of sub-effective doses of opiorphin and bradykinin caused a significant anti-escape effect. The anti-escape effect of bradykinin was not affected by previous administration of WAY-100635. Therefore, the anti-escape effect of opiorphin in the dPAG seems to be mediated by endogenous bradykinin, acting on kinin B2 receptors, which previous results have shown to interact synergistically with MOR in the dPAG to restrain escape in two animal models of panic.
Chemical compounds: Opiorphin (PubChem CID: 25195667); WAY100635 maleate salt (PubChem CID: 11957721); 8-OH-DPAT hydrobromide (PubChem CID: 6917794); Bradykinin (PubChem CID: 439201); HOE-140 (Icatibant) (PubChem CID: 6918173).

• 出版日期2017-10-3