Gly-Pro and Adaptive Reactions in Multicomponent Stress

We report here studies on the effects of the peptide glycylproline (Gly-Pro) on measures of reactivity and adaptive potential on stimulation of the parasympathetic nervous system with carbachol in conditions of sequential exposure to the combined actions of three stress factors: immobilization, surgery, and an injection procedure. Sequential combination of surgery (application of a ligature to the pylorus of the stomach), immobilization, and the procedure of injecting physiological saline on the background of carbachol allowed four types of response in rats to be identified. These variants were characterized by different combinations of levels of corticosterone and different leukocyte subpopulations. All response variants were accompanied by development of stress, as indicated by the adaptation intensity index. The most profound stress reactions were seen in animals after immobilization and surgery and the combination of injection of physiological saline and carbachol. By modulating the parasympathetic compartment of the autonomic nervous system and, probably, a direct influence on the adrenals, Gly-Pro altered the corticosterone content and different leukocyte subpopulations and the adaptation intensity index in multicomponent stress. When peptide was given simultaneously with carbachol, it appeared to act via the resistance (counteraction) pathway of adaption, while when given in advance, before carbachol, it operated via the tolerance (stamina, endurance) pathway.