The long range objective of this project is to apply the techniques of biochemistry to investigate how genes of the nervous system are expressed and regulated. The nervous system is composed of many neurons which interconnect with one another in a precise manner. The diversity of neurons and the nature of their interactions suggest that specific genes or sets of genes are activated in some neurons and not in others. The autonomic nervous system affords a particularly suitable approach to analyzing specific gene expression. The adrenal medulla is part of the autonomic nervous system which is embryologically derived from neurons tissue and which is analogous to postganglionic neurons. The adrenal medulla is a major site of catecholamine biosynthesis as well as the site for synthesis of neuropeptides. One of the specific aims of this proposal is to develop a better understanding of the molecular events regulating the rate controlling enzyme in catecholamine biosynthesis (tyrosine hydroxylase) and the newly discovered peptide which has been named neuropeptide Y. The brain also synthesizes numerous classical neurotransmitters and neuropeptides. Two of the major neuropeptides found in the brain are neuropeptide Y and cholecystokinin. The tools of molecular biology will be used t develop a better understanding of how the gene(s) encoding cholecystokinin are controlled and modulated during development. The information obtained from these studies should also suggest structures for the precursors to human and rat cholecystokinin(s) and potential sties of post-translational processing.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM018849-10
Application #
3151166
Study Section
Biochemistry Study Section (BIO)
Project Start
1976-05-01
Project End
1989-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
10
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Purdue University
Department
Type
Earth Sciences/Resources
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907
Haun, R S; Dixon, J E (1990) A transcriptional enhancer essential for the expression of the rat cholecystokinin gene contains a sequence identical to the -296 element of the human c-fos gene. J Biol Chem 265:15455-63
Haun, R S; Beinfeld, M C; Roos, B A et al. (1989) Establishment of a cholecystokinin-producing rat medullary thyroid carcinoma cell line. Endocrinology 125:850-6
Plisetskaya, E M; Pollock, H G; Elliott, W M et al. (1988) Isolation and structure of lamprey (Petromyzon marinus) insulin. Gen Comp Endocrinol 69:46-55
Brayton, K A; Aimi, J; Qiu, H et al. (1988) Cloning, characterization, and sequence of a porcine cDNA encoding a secreted neuronal and endocrine protein. DNA 7:713-9
Glembotski, C C; Dixon, J E; Gibson, T R (1988) Secretion of atrial natriuretic factor-(1-98) by primary cardiac myocytes. J Biol Chem 263:16073-81
Nichols, R; Lee, T D; Andrews, P C (1988) Pancreatic proglucagon processing: isolation and structures of glucagon and glucagon-like peptide from gene I. Endocrinology 123:2639-45
Shields, P P; Dixon, J E; Glembotski, C C (1988) The secretion of atrial natriuretic factor-(99-126) by cultured cardiac myocytes is regulated by glucocorticoids. J Biol Chem 263:12619-28
Andrews, P C; Pollock, H G; Elliott, W M et al. (1988) Isolation and characterization of a variant somatostatin-14 and two related somatostatins of 34 and 37 residues from lamprey (Petromyzon marinus). J Biol Chem 263:15809-14
Andrews, P C; Alai, M; Cotter, R J (1988) The use of plasma desorption time-of-flight mass spectrometry to screen for products of prohormone processing in crude tissue extracts. Anal Biochem 174:23-31
Andrews, P C; Nichols, R; Dixon, J E (1987) Post-translational processing of preprosomatostatin-II examined using fast atom bombardment mass spectrometry. J Biol Chem 262:12692-9

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