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Bombesin receptor subtypes: Implications in bombesin satiety
Appetite, 1995, 24, 261
Bombesin Receptor Subtypes: Implications in Bombesin Satiety.
Ellen E.
Johns Hopkins University School of Medicine, Baltimore, MD 21205 and Janet L. Guss, St Luke's~Roosevelt Hospital and Columbia University New York, NY 10025, U.S.A. Ladenheim.
Several studies have been carried out to determine the site of action of bombesin(BBS)like peptides in order to elucidate the mechanisms contributing to BBS-induced satiety. Bombesin is a putative satiety agent found in the amphibian. Gastrin-releasing peptide (GRP) and neuromedin B (NMB) are two peptides found in mammals which bear structural and functional similarities to BBS. In the rat, gastrin-releasing peptide (GRP) and neuromedin B (NMB) have been isolated and are both biologically active. BBS has been shown to reduce food intake in rats and humans when administered peripherally; BBS has also suppressed food intake in rats when injected centrally. Peripherally, BBS has reduced food intake when injected intravenously or intraperitoneally, even when animals underwent total diaphragmatic vagotomy. Although dorsal rhizotomy attenuates BBS's effect on food intake, only total subdiaphragmatic vagotomy, dorsal rhizotomy (T3-6) and spinal cord transection (T6) completely abolish the intake-suppressing effect of peripherally injected BBS. This procedure prevents the transmission of sensory information from the gastrointestinal tract to the brain. BBS injection into the rat lateral ventricle also suppresses feeding, but elicits increased motor activity as well. In contrast, injection directly into the fourth ventricle of the CNS in rats suppressed food intake at much lower doses of BBS, and was behaviorally specific, i.e. no behavior other than satiety was exhibited in these animals. Separate receptors with differential affinities for GRP and NMB have been found in the periphery. Pancreatic BBS binding sites have a high affinity for GRP, while esophageal BBS binding sites have a greater affinity for NMB. Both the pancreas and the esophagus have an equal affinity for BBS. There also seem to be receptor distinctions between GRP and NMB in the brain. GRP-preferring receptors were located primarily in the paraventricular and arcuate nuclei, while the ventromedial hypothalamus and thalamus were demonstrated to be NMB-preferring sites. In the spinal trigeminal tract in the caudal hindbrain, receptors for both peptides were found. Injection of NMB directly into the third ventricle reduced food intake, though with less potency than BBS. Therefore, these studies suggest that NMB and GRP have distinct roles within the CNS involved in satiety. Receptor antagonists specific for each subtype are now available and will help to define the contributions of each of these peptides to BBS induced satiety. In order to identify more specific sites of action for NMB and GRP within the aforementioned regions of the brain, several lesions were induced in the area postrema (AP) and the nucleus of the solitary tract (NST). Lesions of the AP and NST abolished the suppression of intake by low-dose, fourth-ventricular administration and attenuated the suppression by peripheral BBS administration. Lesions confined to the AP attenuated the suppression of intake by lower doses of BBS injected into the fourth ventricle but these lesions had no effect on peripheral BBS administration. Since visceral information seems to be an important component for the central effect of BBS-induced satiety, it is possible that peripheral and central information combined at the NST to effect BBS-induced satiety in animals. Muurahainen, N. E., Kissileff, H. R. & Pi-Sunyer, F. X. (1993) Intravenous infusion of bombesin reduces food intake in humans. American Journal of Physiology, 264, R350-4. Ladenheim, E. E. & Ritter, R. C. (1988) Low-dose fourth ventricular bombesin selectively suppresses food intake. American Journal of Physiology, 255, R988-92. Flynn, F. W. (1989) Fourth ventricular bombesin injection suppresses ingestive behaviors in rats. American Journal of Physiology, 262, R590-6. Von Schrenck, T., Heinz-Erian, P., Moran, T. H., Mantey, S. A., Gardner, J. D. & Jensen, R. T. (1989) Neuromedin B receptor in esophagus: evidence for subtypes of bombesin receptors. American Journal of Physiology, 256, G747-58. Ladenheim, E. E. & Ritter, R. C. (1993). Caudal hindbrain participation in the suppression of feeding by central and peripheral bombesin. American Journal of Physiology, 264, R 1229-34.
Summary of presentation for the Columbia University Seminar on Appetitive Behavior, 8 September 1994; Harry Kissileff, Chairman. Sponsored in part by Hoffmann-LaRoche, Miles, Inc./Bayer AG, Pepsico, and the New York Obesity Research Center, St Luke's/Roosevelt Hospital. 0195-6663/95/030261 +01 $08.00/0
© 1995 Academic Press Limited
Bombesin Receptor Subtypes: Implications in Bombesin Satiety.
Ellen E.
Johns Hopkins University School of Medicine, Baltimore, MD 21205 and Janet L. Guss, St Luke's~Roosevelt Hospital and Columbia University New York, NY 10025, U.S.A. Ladenheim.
Several studies have been carried out to determine the site of action of bombesin(BBS)like peptides in order to elucidate the mechanisms contributing to BBS-induced satiety. Bombesin is a putative satiety agent found in the amphibian. Gastrin-releasing peptide (GRP) and neuromedin B (NMB) are two peptides found in mammals which bear structural and functional similarities to BBS. In the rat, gastrin-releasing peptide (GRP) and neuromedin B (NMB) have been isolated and are both biologically active. BBS has been shown to reduce food intake in rats and humans when administered peripherally; BBS has also suppressed food intake in rats when injected centrally. Peripherally, BBS has reduced food intake when injected intravenously or intraperitoneally, even when animals underwent total diaphragmatic vagotomy. Although dorsal rhizotomy attenuates BBS's effect on food intake, only total subdiaphragmatic vagotomy, dorsal rhizotomy (T3-6) and spinal cord transection (T6) completely abolish the intake-suppressing effect of peripherally injected BBS. This procedure prevents the transmission of sensory information from the gastrointestinal tract to the brain. BBS injection into the rat lateral ventricle also suppresses feeding, but elicits increased motor activity as well. In contrast, injection directly into the fourth ventricle of the CNS in rats suppressed food intake at much lower doses of BBS, and was behaviorally specific, i.e. no behavior other than satiety was exhibited in these animals. Separate receptors with differential affinities for GRP and NMB have been found in the periphery. Pancreatic BBS binding sites have a high affinity for GRP, while esophageal BBS binding sites have a greater affinity for NMB. Both the pancreas and the esophagus have an equal affinity for BBS. There also seem to be receptor distinctions between GRP and NMB in the brain. GRP-preferring receptors were located primarily in the paraventricular and arcuate nuclei, while the ventromedial hypothalamus and thalamus were demonstrated to be NMB-preferring sites. In the spinal trigeminal tract in the caudal hindbrain, receptors for both peptides were found. Injection of NMB directly into the third ventricle reduced food intake, though with less potency than BBS. Therefore, these studies suggest that NMB and GRP have distinct roles within the CNS involved in satiety. Receptor antagonists specific for each subtype are now available and will help to define the contributions of each of these peptides to BBS induced satiety. In order to identify more specific sites of action for NMB and GRP within the aforementioned regions of the brain, several lesions were induced in the area postrema (AP) and the nucleus of the solitary tract (NST). Lesions of the AP and NST abolished the suppression of intake by low-dose, fourth-ventricular administration and attenuated the suppression by peripheral BBS administration. Lesions confined to the AP attenuated the suppression of intake by lower doses of BBS injected into the fourth ventricle but these lesions had no effect on peripheral BBS administration. Since visceral information seems to be an important component for the central effect of BBS-induced satiety, it is possible that peripheral and central information combined at the NST to effect BBS-induced satiety in animals. Muurahainen, N. E., Kissileff, H. R. & Pi-Sunyer, F. X. (1993) Intravenous infusion of bombesin reduces food intake in humans. American Journal of Physiology, 264, R350-4. Ladenheim, E. E. & Ritter, R. C. (1988) Low-dose fourth ventricular bombesin selectively suppresses food intake. American Journal of Physiology, 255, R988-92. Flynn, F. W. (1989) Fourth ventricular bombesin injection suppresses ingestive behaviors in rats. American Journal of Physiology, 262, R590-6. Von Schrenck, T., Heinz-Erian, P., Moran, T. H., Mantey, S. A., Gardner, J. D. & Jensen, R. T. (1989) Neuromedin B receptor in esophagus: evidence for subtypes of bombesin receptors. American Journal of Physiology, 256, G747-58. Ladenheim, E. E. & Ritter, R. C. (1993). Caudal hindbrain participation in the suppression of feeding by central and peripheral bombesin. American Journal of Physiology, 264, R 1229-34.
Summary of presentation for the Columbia University Seminar on Appetitive Behavior, 8 September 1994; Harry Kissileff, Chairman. Sponsored in part by Hoffmann-LaRoche, Miles, Inc./Bayer AG, Pepsico, and the New York Obesity Research Center, St Luke's/Roosevelt Hospital. 0195-6663/95/030261 +01 $08.00/0
© 1995 Academic Press Limited