Investigation of cerebrovascular activity of new GABA-derived short peptides

Abstract

Based on the important role of endogenous substances in the cerebral blood flow regulation, the cerebrovascular activity of new synthesized short peptides of γ-aminobutyric acid (GABA) and pyroglutamate has been investigated, considering the development of new drugs for the correction of cerebral circulation. Taking into account the proven ability to increase cerebral blood flow of γ-aminobutyric acid and its endogenous metabolites, such as gamma butyrolactone, gamma hydroxybutyric acid, pyrrolidone, pyroglutamic acid, as well as synthetic analogues, such as picamilon, the influence of pyroglutamyl GABA, pyroglutamyl GABA ethyl ester, pyroglutamyl diGABA was observed on local brain blood flow in a state of impaired cerebral circulation. The model of cerebral chronic hypoperfusion generated by right common carotid artery occlusion was used on rats weighing 180-240 g, under anesthesia with chloral hydrate (400 mg/kg). The investigated peptides were administered at a dose of 20 mg/kg, intraperitoneally. Cerebral blood flow changes were detected by laser Doppler flowmetry. The conducted experiment revealed differences between the cerebrovascular activities of the studied short peptides. Thus, it was demonstrated that pyroglutamyl GABA exhibits а high ability to increase local cerebral blood flow, stimulating cerebral circulation by 65,2 %, compared with the value of hypoperfusion by right common carotid artery occlusion, after 40 minutes of injection. However, no essential changes in the studied indicator were recorded for pyroglutamyl GABA ethyl ester and pyroglutamyl diGABA. The obtained data indicate that the prolongation of the short peptide chain leads to a decrease in cerebrovascular activity and opens up new perspectives for the development of pyroglutamyl GABA dipeptide as a promising agent for the correction of cerebral circulation