Tissue-specific processing of cocaine- and amphetamine-regulated transcript peptides in the rat

Cocaine- and amphetamine-regulated transcript (CART) is a recently discover ed hypothalamic peptide regulated by leptin and with a potent appetite-supp ressing activity. In the rat, the CART gene encodes a peptide of 116 amino acid residues (or a splice variant 13 residues longer). The predicted signa l sequence is 27 amino acid residues, resulting in a prohormone of 89 resid ues. The CART prohormone contains several potential posttranslational proce ssing sites in the form of mono- and dibasic sequences, In the present stud y we have purified CART peptides from extracts of adrenal gland, hypothalam us! nucleus accumbens, and pituitary gland (anterior and neurointermediate lobe) of the rat and determined the peptide structures by using microsequen cing and mass spectrometry. In none of the tissues examined the long splice variant was found. From the adrenal gland, the CART(1-89) and CART(10-89) peptides Here isolated, in contrast to the hypothalamus and nucleus accumbe ns, from which the shorter form peptides CART(42-89) and CART(49-89) were p urified. From the anterior lobe of the pituitary gland, CART(42-89) was iso lated, in contrast to the neurointermediate robe, which contains only CART( 49-89). This tissue-specific processing indicates that CART peptides may ha ve different biological functions in the periphery and in the central nervo us system.