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Distribution of pre‐pro‐glucagon and glucagon‐like peptide‐1 receptor messenger RNAs in the rat central nervous system

Glucagon‐like peptide‐1 (GLP‐1) is derived from the peptide precursor pre‐pro‐glucagon (PPG) by enzymatic cleavage and acts via its receptor, glucagon‐like peptide‐1 receptor (GLP‐1R). By using riboprobes complementary to PPG and GLP‐1R, we described the distribution of PPG and GLP‐1R messenger RNAs (mRNAs) in the central nervous system of the rat. PPG mRNA‐expressing perikarya were restricted to the nucleus of the solitary tact or to the dorsal and ventral medulla and olfactory bulb. GLP‐1R mRNA was detected in numerous brain regions, including the mitral cell layer of the olfactory bulb; temporal cortex; caudal hippocampus; lateral septum; amygdala; nucleus accumbens; ventral pallium; nucleus basalis Meynert; bed nucleus of the stria terminalis; preoptic area; paraventricular, supraoptic, arcuate, and dorsomedial nuclei of the hypothalamus; lateral habenula; zona incerta; substantia innominata; posterior thalamic nuclei; ventral tegmental area; dorsal tegmental, posterodorsal tegmental, and interpeduncular nuclei; substantia nigra, central gray; raphe nuclei; parabrachial nuclei; locus ceruleus, nucleus of the solitary tract; area postrema; dorsal nucleus of the vagus; lateral reticular nucleus; and spinal cord. These studies, in addition to describing the sites of GLP‐1 and GLP‐1R synthesis, suggest that the efferent connections from the nucleus of the solitary tract are more widespread than previously reported. Although the current role of GLP‐1 in regulating neuronal physiology is not known, these studies provide detailed information about the sites of GLP‐1 synthesis and potential sites of action, an important first step in evaluating the function of GLP‐1 in the brain. The widespread distribution of GLP‐1R mRNA‐containing cells strongly suggests that GLP‐1 not only functions as a satiety factor but also acts as a neurotransmitter or neuromodulator in anatomically and functionally distinct areas of the central nervous system. J. Comp. Neurol. 403:261–280, 1999. © 1999 Wiley‐Liss, Inc.