NEUROTRANSMITTER REGULATION OF BETA-ENDORPHIN SECRETION

点击翻译按钮获取中文摘要

The specific aims of this proposal are to determine the roles of brain monoamine and acetylcholine neurotransmitters in regulating the physiologic secretion of pituitary Beta-endorphin 1-31 (B-END1-31) and structurally related peptides in the rat. Two approaches will be used in this investigation. One will involve electrolytic lesion techniques (raphe, locus coeruleus) and the systematic use of pharmacologic agents (receptor agonists and antagonists) to examine the control which brain serotonin, dopamine, norepinephrine and acetylcholine neurons may exert over the basal and stimulated secretion of B-END-like peptides. The drugs to be tested are those which best discriminate between specific functions of receptor subtypes (e.g. serotonin 1 vs serotonin 2; dopamine 1 vs dopamine 2); as necessary these agents will be administered directly into the CNS to limit their actions within the brain. The effects of experimental treatments on plasma levels of total B-END-like immunoreactivity, as well as levels of individual peptides comprising this immunoreactivity will be determined. Specifically, B-END1-31 and B-END1-27, their acetylated forms, and Beta-lipotropin will be isolated from plasma extracts by cation exchange (SP-Sephadex) and high pressure liquid chromatography and subsequently quantified by immunoassay. The second approach in this investigation will correlate the regional turnover of dopamine, norepinephrine and serotonin in the hypothalamus, and dopamine turnover in the pars intermedia, with the physiologic release of B-END-like peptides. These studies will better define the neural mechanism regulating the secretion of B-END-like peptides. Based on the distinctive forms of B-END peptides secreted by the pars distalis and pars intermedia in vitro, chromatographic analysis of B-END-like peptides in plasma may reveal the particular lobe of the pituitary from which B-END-LI is secreted by a given stimulus. Furthermore, these studies may suggest pharmacologic strategies for selectively controlling the secretion of B-END-like peptides in man, approaches which could be useful in the treatment of clinical pain. Ultimately it is hoped that knowledge of the regulation of B-END-like peptides will lead to a greater understanding of the physiologic functions of these hormones and the pituitary gland.