This research proposal is designed to study several aspects of brain peptide functions by use of a variety of complementary experimental techniques. Experiments will focus on the role of somatostatin in pituitary regulation and on its postulated effects as a neurotransmitter in brain. Five separate but interrelated experimental approaches will be used: 1) The role of somatostatin, biogenic amine neurotransmitters and other brain peptides in episodic growth hormone(GH) secretion will be investigated in the unanesthetized, cannulated rat. 2) Factors that determine somatostatin release from brain tissue will be studied in vitro by use of a perifusion system developed in our laboratory. 3) The function of cerebrospinal fluid (CSF) as a potential system for distribution of peptides to brain tissues will be investigated by measurement of endogenous somatostatin secretion into CSF in the unanesthetized rabbit and by analysis of the fate of exogenously administered cold and radioactive-labeled somatostatin. Studies in the awake sheep will determine interrelationships between blood and CSF levels of GH, prolactin (PRL) and somatostatin. 4) The anatomic and physiologic significance of several peptides in the retina will be investigated. 5) The distribution and concentration of peptides in normal and abnormal human brain tissue will be determined. These experimental techniques will provide new information concerning the function of small-molecular weight peptides in brain function.
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