Panicolytic-like action of bradykinin in the dorsal periaqueductal gray through μ-opioid and B2-kinin receptors
| Autor: | Jhonatan Christian Maraschin, Vanessa Scalco Gama, Caio César Sestile, Elisabeth Aparecida Audi, Frederico Guilherme Graeff, Hélio Zangrossi |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Agonist medicine.medical_specialty Captopril Receptor Bradykinin B2 medicine.drug_class Receptors Opioid mu Bradykinin Angiotensin-Converting Enzyme Inhibitors (+)-Naloxone Pharmacology Periaqueductal gray 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Escape Reaction Opioid receptor Internal medicine Bradykinin B2 Receptor Antagonists SOMATOSTATINA medicine Animals Periaqueductal Gray Rats Wistar Enkephalin Ala(2)-MePhe(4)-Gly(5) Kinin Panic Analgesics Opioid DAMGO 030104 developmental biology Endocrinology Anti-Anxiety Agents chemistry Opioid Somatostatin 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 0028-3908 |
| Popis: | A wealth of evidence has shown that opioid and kinin systems may control proximal defense in the dorsal periaqueductal gray matter (dPAG), a critical panic-associated area. Studies with drugs that interfere with serotonin–mediated neurotransmission suggest that the μ-opioid receptor (MOR) synergistically interacts with the 5-HT 1A receptor in the dPAG to inhibit escape, a panic-related behavior. A similar inhibitory effect has also been reported after local administration of bradykinin (BK), which is blocked by the non-selective opioid receptor antagonist naloxone. The latter evidence, points to an interaction between BK and opioids in the dPAG. We further explored the existence of this interaction through the dPAG electrical stimulation model of panic. We also investigated whether intra-dPAG injection of captopril, an inhibitor of the angiotensin-converting enzyme (ACE) that also degrades BK, causes a panicolytic-like effect. Our results showed that intra-dPAG injection of BK inhibited escape performance in a dose-dependent way, and this panicolytic-like effect was blocked by the BK type 2 receptor (B2R) antagonist HOE-140, and by the selective MOR antagonist CTOP. Conversely, the panicolytic-like effect caused by local administration of the selective MOR agonist DAMGO was antagonized by pre-treatment with either CTOP or HOE-140, indicating cross-antagonism between MOR and B2R. Finally, intra-dPAG injection of captopril also impaired escape in a dose-dependent way, and this panicolytic-like effect was blocked by pretreatment with HOE-140, suggesting mediation by endogenous BK. The panicolytic-like effect of captopril indicates that the use of ACE inhibitors in the clinical management of panic disorder may be worth exploring. |
| Databáze: | OpenAIRE |
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