Behavioral effects of Bj-PRO-7a, a proline-rich oligopeptide from Bothrops jararaca venom

Abstract

The heptapeptide Bj-PRO-7a, isolated and identified from Bothrops jararaca (Bj) venom, produces antihypertensive and other cardiovascular effects that are independent on angiotensin converting enzyme inhibition, possibly relying on cholinergic muscarinic receptors subtype 1 (M1R). However, whether Bj-PRO-7a acts upon the central nervous system and modifies behavior is yet to be determined. Therefore, the aims of this study were: i) to assess the effects of acute administration of Bj-PRO-7a upon behavior; ii) to reveal mechanisms involved in the effects of Bj-PRO-7a upon locomotion/exploration, anxiety, and depression-like behaviors. For this purpose, adult male Wistar (WT, wild type) and spontaneous hypertensive rats (SHR) received intraperitoneal injections of vehicle (0.9% NaCl), diazepam (2 mg/kg), imipramine (15 mg/kg), Bj-PRO-7a (71, 213 or 426 nmol/kg), pirenzepine (852 nmol/kg), α-methyl-DL-tyrosine (200 mg/kg), or chlorpromazine (2 mg/kg), and underwent elevated plus maze, open field, and forced swimming tests. The heptapeptide promoted anxiolytic and antidepressant-like effects and increased locomotion/exploration. These effects of Bj-PRO-7a seem to be dependent on M1R activation and dopaminergic receptors and rely on catecholaminergic pathways.

Activation of M1 muscarinic acetylcholine receptors by proline-rich oligopeptide 7a (<EDGPIPP) from Bothrops jararaca snake venom rescues oxidative stress-induced neurotoxicity in PC12 cells

“…Studies have revealed that PRO-7a is an M1 mAChR agonist, which is of critical relevance given the extensive research that focused on finding such a ligand [ 24 , 57 , 58 ]. The peptide specifically activates [Ca 2+ ] I transients in CHO and neuronal P19 cells expressing the M1 mAChR subtype, which are inhibited in cells pretreated with the M1 mAChR specific antagonist pirenzepine [ 24 ].…”

“…The peptide specifically activates [Ca 2+ ] I transients in CHO and neuronal P19 cells expressing the M1 mAChR subtype, which are inhibited in cells pretreated with the M1 mAChR specific antagonist pirenzepine [ 24 ]. The PRO-7a also improved anxiolytic and antidepressant-like actions in rats, as well as increased mobility and exploration, and these effects appear to be partially dependent on M1 mAChR activation [ 57 , 58 ]. Then, since PC12 cells express the M1 mAChR endogenously [ 59 , 60 ], we investigated the potential involvement of cholinergic receptors in PRO-7a-mediated neuroprotection via activation of M1 mAChR, using the competitive antagonist DCH [ 39 ] to suppress receptor activity in our neuroprotective assay with PRO-7a in PC12 cells.…”

Behavioral effects of a low molecular weight peptide fraction from Phaseolus vulgaris in rats

“…Methods to test behavior were performed as previously described ( 7 ). All experiments were performed in a quiet and dimly illuminated room.…”

Studies about Snake Peptides: a Review about Brazilian Contribution

“…This same peptide has been linked by Brazilian researchers to the normalization of endothelial dysfunction related to preeclampsia, which is a disease characterized by hypertension during pregnancy, that is, the peptide is useful as an antihypertensive in cases of preeclampsia and can be effective for new treatments against the disease [90]. Still about B. jararaca peptides rich in proline, the properties of Bj-PRO 7a were also investigated by Brazilian researchers [91]. The peptides called Bj-PROs are recognized for being inhibitors of the angiotensin-converting enzyme and having pharmacological action, which resulted in the antihypertensive drug, Captopril [92].…”