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Tissue-specific processing of cocaine- and amphetamine-regulated transcript peptides in the rat
L Thim1, P Kristensen, P F Nielsen
1Health Care Discovery, Novo Nordisk A/S, DK-2880 Bagsvaerd, Denmark. lth@novo.dk
Summary
Cocaine- and amphetamine-regulated transcript (CART) peptides are processed differently in various rat tissues. This tissue-specific processing suggests distinct roles for CART peptides in the central nervous system and periphery.
Area of Science:
- Neuroendocrinology
- Molecular Biology
- Peptide Chemistry
Background:
- Cocaine- and amphetamine-regulated transcript (CART) is a hypothalamic peptide known for appetite suppression.
- CART is regulated by leptin and originates from a gene encoding a 116-amino acid peptide or a 13-amino acid longer splice variant.
- The CART prohormone has potential post-translational processing sites.
Purpose of the Study:
- To investigate the tissue-specific processing and structure of CART peptides in rat tissues.
- To identify the specific CART peptide forms present in the adrenal gland, hypothalamus, nucleus accumbens, and pituitary gland.
Main Methods:
- Purification of CART peptides from various rat tissue extracts.
- Determination of peptide structures using microsequencing and mass spectrometry.
Main Results:
- The long splice variant of CART was not detected in any examined tissues.
- Adrenal gland yielded CART(1-89) and CART(10-89).
- Hypothalamus and nucleus accumbens contained shorter forms: CART(42-89) and CART(49-89).
- Anterior pituitary contained CART(42-89), while the neurointermediate lobe contained only CART(49-89).
Conclusions:
- CART peptides undergo tissue-specific post-translational processing in rats.
- These distinct processing patterns suggest specialized biological functions for CART peptides in different tissues, including the central nervous system and periphery.