Effects Of Endogenous Peptides Research Articles

Effect of endogenous peptides on the currents Of NMDA- AND AMPA-receptors of neurons of the cortex, hippocampus and cerebellum of rat brain

The obtained results show that endogenous peptides play an important role in the regulation of the glutamatergic mediator system of the brain. They act in extremely low concentrations, starting at 1 × 10–14 M, their effects are concentration-dependent and reversible, thus indicating the exclusive specificity of the corresponding receptors. The range of their influence on responses of postsynaptic glutamate receptors is rather narrow and, as a rule, does not exceed 60-70% of control. We have demonstrated for the first time that CLIP blocks NMDA receptors and potentiates AMPA receptors in a wide range of concentrations (6 orders of magnitude); this is very important for manifestation of memory-stimulating effect. Somatostatin blocking NMDA receptors and potentiating AMPA receptors, also plays an important role in the mechanisms of memory formation. Obviously, there is a great similarity in the action of both peptides on AMPA and NMDA receptors. Thus our results provide the first information about regulation of including cognitive processes and memory mechanisms by endogenous compounds. This mechanism particularly involves regulation of AMPA and NMDA receptors in the brain.

Endogenous Vasoactive Peptides and the Human Vagina—A Molecular Biology and Functional Study

Endogenous peptides, such as vasoactive intestinal polypeptide (VIP), C-type natriuretic peptide (CNP), and bradykinin (BK), have been proposed to play a role in the female sexual arousal response by exerting relaxation of clitoral, labial, and vaginal smooth muscle. While the effects of endogenous peptides on the human male erectile tissue have already been described, only very few studies have been conducted to investigate the peptidergic control of female genital tissues, including the vagina. To elucidate the expression of mRNA specifically encoding for peptide receptors in the human vagina and the effects of VIP, CNP, and BK on the tension induced by endothelin-1 (ET-1) of isolated human vaginal wall smooth muscle. The production of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in response to exposure of the tissue to the peptides was also measured. The expression of mRNA encoding for receptor proteins specific for VIP, CNP, and BK were investigated by means of molecular biology (reverse transcriptase polymerase chain reaction [RT-PCR] analysis). Using the organ bath technique, the effects of VIP, CNP, and BK (0.1 nM to 1 µM) on the tension induced by 0.1 µM ET-1 of human vaginal strips were investigated. The tissue was also exposed to three different concentrations of VIP, CNP, and BK (0.01 µM, 0.1 µM, 1 µM) and the production of cAMP and cGMP determined by means of radioimmunoassays. Characterize the expression of peptide receptors in the human vagina and measure the relaxation exerted by BK, CNP, and VIP on the contraction induced by ET-1 of isolated human vaginal tissue. In addition, the effects of the peptides on the production of cAMP and cGMP were also elucidated. RT-PCR analysis revealed the expression of mRNA transcripts encoding for the VIP receptors VIP1R/vasoactive intestinal polypeptide receptor type 1 (VPAC1) and VIP2R/VPAC2, CNP receptors natriuretic peptide receptor type A (NPRA), natriuretic peptide receptor type B (NPRB) and natriuretic peptide receptor type C (NPRC), and BK receptor B2R. The tension induced by ET-1 was reversed by the peptides with the following rank order of efficacy: BK (21.7%) > VIP (20.9%) > CNP (13.3%). The relaxing effects of VIP and BK were paralleled by a 4.8-fold and fivefold increase in cAMP, while the production of cGMP was stimulated 38-fold and 119-fold in the presence of CNP or BK, respectively. Our results are in support of the hypothesis that endogenous peptides may contribute to the control of human vaginal smooth muscle tone through the involvement of the cyclic nucleotide-dependent pathways.

Dissociation of the Peptide/MHC Class I Complex: pH Dependence and Effect of Endogenous Peptides on the Activation Energy

Dansylated peptides were used to characterize the dissociation of peptides from a recombinant class I major histocompatibility complex protein. Dissociation of endogenous, low-affinity peptides from the class I molecule Kd had an activation energy of 6.78 ± 0.64 kcal/mole in the 14 to 26 °C temperature range, but there was a break in the Arrhenius plot between 12 and 14 °C. Dissociation of a dansylated, high-affinity peptide had an activation energy of 20.24 ± 1.69 kcal/mole, and there was similarly a break in the plot. Both direct interactions between peptide and the class I heavy chain and indirect effects of the peptide affinity on the extent of light chain association with heavy chain may contribute to the difference in activation energies, while the break in the Arrhenius plots implies a temperature-dependent conformational change. Dissociation was also slowest at neutral pH, but the peptide/class I complex dissociated rapidly at pH greater than 9 and less than 5, suggesting that endocytosed class I proteins would most likely lose their bound peptides at the acidic pH of endosomes.