pituitrin and argipressin-(4-8)

Vasopressin (VP) is axonally distributed in many brain structures, including the ventral hippocampus. Picogram quantities of VP injected into the hippocampus improve the passive avoidance response of rats, presumably by enhancing memory processes. Vasopressin is metabolized by the brain tissue into shorter peptides, such as [pGlu4,Cyt6]VP(4-9) and [pGlu4,Cyt6]VP(4-8), which preserve the behavioral activity but lose the peripheral activities of the parent hormone. Using brain slices, we investigated whether VP or VP(4-8) affects excitatory postsynaptic potentials (EPSPs) and/or membrane responses to depolarization in neurons of the CA1/subiculum of the ventral hippocampus. The EPSPs were evoked by stimulating the striatum radiatum of the CA1 field; the membrane responses were elicited by current injections. Exposure of slices for 15 min to 0.1 nM solution of these peptides resulted in an increase in the amplitude and slope of the EPSPs in 21 neurons (67%) tested. No consistent change in either the resting membrane potential or the input resistance of the neurons was observed. The peptide-induced increase in EPSPs reached a maximum 30-45 min after peptide application. In 14 of these neurons (66%), the peptide-induced increase in EPSPs remained throughout the entire 60-120 min washout period. In the remaining 7 neurons (33%), the initial increase in EPSPs amplitude was followed by a gradual decline to the pre-administration level. The increase in EPSP amplitude was often, but not always, associated with a decrease in the threshold and increase in the number of action potentials in response to depolarizing current injection. Suppression of GABAA receptor-mediated inhibition and N-methyl-D-aspartate (NMDA) receptor-mediated excitation did not prevent the effects of VP and VP(4-8) on the EPSP amplitude or the threshold for action potentials. The results demonstrate that 0.1 nM concentrations of these neuropeptides can elicit a long-lasting enhancement of the excitability of CA1/subiculum neurons of the ventral hippocampus to excitatory, glutamatergic synaptic input. This novel action of VP and its metabolite in the ventral hippocampus may be the physiological action, mediating the memory-enhancing effect of these peptides.

Topics: Animals; Arginine Vasopressin; Evoked Potentials; Hippocampus; Hormone Antagonists; In Vitro Techniques; Long-Term Potentiation; Male; Membrane Potentials; Neurons; Peptide Fragments; Rats; Rats, Wistar; Receptors, Neurotransmitter; Vasopressins

The paper mainly stresses on the effect of argipressin (Arg), 2-destyrosyl-3-desphenyl-alanyl-9-desglycyl-amide-Arg (Arg4-8), [1-deaminopenicillamine, 2-(o-methyl)tyrosine]-Arg (DPArg) and Arg antiserum on corticotropin releasing hormone (CRH) contents in median eminence (ME) and the level of plasma corticosterone after injected into the third ventricle of rats. The results show: 1) the CRH contents in ME significantly reduced with icv 100, 200, and 800 ng of Arg; 2) 100 ng of Arg4-8 and Arg antiserum (2 microliters, 1:1 diluted with 0.9% saline) increased CRH contents in ME and enhanced plasma corticosterone; 3) DPArg had no effect on CRH level but blocked the inhibitory role of Arg on central CRH. These results suggest that Arg acts as an inhibitory factor in regulating central CRH level and V1 receptor is involved.

Topics: Animals; Arginine Vasopressin; Corticosterone; Corticotropin-Releasing Hormone; Immune Sera; Male; Median Eminence; Peptide Fragments; Rats; Vasopressins