Variations in the rates of neuropeptide synthesis and release are to be expected for all neuroendocrine systems. Nerve terminal compartmentation (differential distribution of different aged granules with respect to release) will interact with the kinetics of precursor biosynthesis, processing and release to yield complex variations in the mixture of biologically active peptides secreted. These variations will not be predictable without a knowledge of both the compartmentation characteristics of the nerve terminal and the kinetics of synthesis, processing and release. The experiments proposed here seek a precise definition of these complex properties in order to better understand the possible physiological role of the peptidergic neuron. Two simple nerve terminal preparations will be studied; the neural lobe of the rat pituitary and the sinus gland of the land crab. The major experimental approach will be to use HPLC analysis of the relative proporations of the products of partial proteolysis in the secretory granule to determine the kinetic history or """"""""age"""""""" of a secretory granule population. The probability of secretory granule release as a function of secretory granule age (compartmentation) will be defined in the neural lobe by determining by HPLC the ratios of the oxytocin neurophysins throughout density gradient granule separations in neural lobes from control, 1, 2, 3 and 5 day dehydrated rats. A similar definition of compartmentation in the sinus gland will be based upon HPLC determination of the partial proteolysis products of the sinus gland H peptide in density gradient separations. Further experiments will define synthesis rates, enzymatic processing rates and the peptide content of release in both systems. Taken together, the data will provide a comprehensive description of factors governing variation in peptide content for two chemically simple neurosecretory systems. The data will then be used to predict variations occurring in more complex systems by mathematical modeling of the effect of compartmentation on variations in relative amounts of released peptides with complex processing situations. The approach is planned to yield an understanding of how the biochemical properties of the secretory neuron are related to its function in the transmission of neural and endocrine information.
| Zierer, R (1991) Impact of ether anesthesia on the hypophyseal content of oxytocin neurophysin I and II: a comparative study with ketamine in the rat. Life Sci 49:1391-7 |
