Immunochemical and immunocytochemical techniques have been used to identify and characterize glucagon-related peptides of the rat central nervous system. These peptides show immunoreactivity with antiglucagon sera directed towards the central portion of the hormone, but not with antisera specific for the free COOH terminus of glucagon. Highest concentrations were found in hypothalamus (6.1 i 1.6 ng/g wet weight) although lower amounts (approximately 2 ng/g) were found in cortex, thalamus, cerebellum, and brain stem. During recent years, a number of intestinal peptides, including substance P (1, 2), vasoactive intestinal peptide (3, 4), and cholecystokinin (5-7), have been identified within the mammnalian brain. Immunoreactive and biologically active pancreatic insulin has also been identified in central nervous tissue of the rat and has been localized, in part, to cells in the olfactory lobe and hypothalamus (8). Conversely, somatostatin (9) and thyrotropin-releasing hormone (10), peptides originally identified in the hypothalamus, have now been found in pancreatic islets. Although in many cases the anatomical diversity of these peptides has yet to be explained functionally, these findings emphasize a close relationship among peptides of the nervous system and those of the pancreas and gastrointestinal tract. Peptides related to pancreatic glucagon occur in several tissues of the body and represent an unusual group of proteolytically modified forms: although gastric glucagon appears to be identical to the 29-residue hormone isolated from pancreas (11), intestinal glucagon-like peptides have higher molecular weights and contain the structure of the hormone extended from its NH2 and COOH termini (12-16). By structural (14, 15), immunocytochemical (16), and biosynthetic (17, 18) criteria, it appears that these larger peptides represent incompletely processed forms of proglucagon. The mapping of biological tissues for these glucagon-containing peptides thus permits an assessment of selective posttranslational modificationThe publication costs of this article were defyayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. 6229as well as an examination of specific gene expression or cellular uptake. This report describes the identification and localization of higher molecular weight forms of glucagon within the brain of the rat. These peptides, like their intestinal counterparts, appear to have both NH2-terminal and COOH-terminal extensions on the glucagon sequence and probably result from a limited posttranslational modification of the glucagon ptcursor. While this work was in progress, two short reports on the subject appeared (19,20).
MATERIALS AND METHODSAntisera and Radioimmunoassays. Three antisera directed against pancreatic glucagon were used in the studies reported here. Antiserum NS (15, 21) is a low-titer serum prepared in a chicken by using a glucagon-albumin conjugate. It reacts well with ...