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Neuropeptide Y-like immunoreactivity in adrenaline cells of adrenal medulla and in tumors and plasma of pheochromocytoma patients
Authors:J M Lundberg  T H?kfelt  A Hemsén  E Theodorsson-Norheim  J Pernow  B Hamberger  M Goldstein
Institution:1. Faculty of Dentistry, McGill University, Montreal, Quebec H3A 0C7, Canada;2. Faculty of Medicine, McGill University, Montreal, Quebec H3G 1Y6, Canada;3. Genetics Unit, Shriners Hospital for Children, Montreal, Quebec H3G 1A6, Canada;1. Division of Endocrinology, University of Miami Miller School of Medicine, Miami, FL, United States;2. Division of Endocrinology, Stanford University School of Medicine, Stanford, CA, United States;1. Goldman School of Dental Medicine, Boston University, Boston, MA 02118, USA;2. Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, 60596 Frankfurt am Main, Germany;1. Quantitative Systems Pharmacology, Early Clinical Development, Worldwide Research, Development and Medical, Pfizer, Cambridge, MA 02139, USA;2. Biomedical Engineering Department, Rutgers University, Piscataway, NJ 08854;3. Chemical & Biochemical Engineering Department, Rutgers University, Piscataway, NJ 08854;4. Department of Surgery, Rutgers-RWJMS, Piscataway, NJ 08854
Abstract:The occurrence of neuropeptide Y (NPY)-like immunoreactivity (LI) in the adrenal gland of several species as well as in tumor tissue and plasma from pheochromocytoma patients was investigated. NPY-LI was present in chromaffin cells of the adrenaline type in all species investigated except in the pig, as demonstrated by a colocalization of NPY-LI and the adrenaline-synthetizing enzyme phenylethanolamine N-methyltransferase (PNMT). NPY-LI in the adrenaline cells of the cat was clearly separated from the neurotensin-LI in the noradrenaline dopamine-beta-hydroxylase-positive, PNMT-negative cells. NPY-LI seems to co-exist with enkephalin-like material in the chromaffin cells. In addition, NPY-LI was present in nerves both within the adrenal cortex and medulla. The highest levels of NPY-LI were found in mouse and cat, while only a very low amount of NPY-LI was present in the pig adrenal. Characterization of the adrenal NPY-LI by reversed-phase high-performance liquid chromatography revealed that the main peak was similar to porcine NPY. In addition, two minor peaks of NPY-LI were present. High levels of NPY-LI were found in plasma and tumors from the pheochromocytoma patients. During manipulation of the tumors upon surgical removal, there was a marked increase in plasma NPY-LI in parallel with the raise in catecholamines and in blood pressure. At least two forms of NPY-LI were present in plasma and tumor extracts from pheochromocytoma patients with the main peak corresponding to porcine NPY. Since NPY exerts vasoconstrictor effects, it may be postulated that NPY contributes to the adrenal cardiovascular response and to the hypertension seen in pheochromocytoma patients.
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