Effects of long-term infusion of anorexic concentrations of islet amyloid polypeptide on neurotransmitters and neuropeptides in rat brain

被引:15
作者
Arnelo, U [1 ]
Herrington, MK
Theodorsson, E
Adrian, TE
Reidelberger, R
Larsson, J
Marcusson, J
Strömmer, L
Ding, XZ
Permert, J
机构
[1] Huddinge Univ Hosp, Karolinska Inst, Dept Surg, Arvid Wretlind Lab Metab Res, S-14186 Huddinge, Sweden
[2] Linkoping Univ, Univ Hosp, Dept Clin Chem, S-58185 Linkoping, Sweden
[3] Linkoping Univ, Univ Hosp, Dept Geriatr Med, S-58185 Linkoping, Sweden
[4] Creighton Univ, Sch Med, Dept Biomed Sci, Omaha, NE 68178 USA
关键词
brain; islet amyloid polypeptide; monoamine; neuropeptide; satiety; body weight;
D O I
10.1016/S0006-8993(00)03070-5
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Islet amyloid polypeptide (IAPP or amylin) potently reduces food intake in rats at or near physiological concentrations. Although the mechanisms of action of IAPP are not understood, the brain is a suggested site. Changes in hypothalamic and striatal neurotransmission have been reported following acute systemic administration of a pharmacological concentration of IAPP In the current study, we evaluated the effects of chronic administration of low doses of IAPP on satiety-related neurotransmitters and neuropeptides in the hypothalamus, hippocampus, striatum, left cortex, and right cortex of the rat. Doses of 0, 5 and 25 pmol IAPP/kg-min were administered subcutaneously for 2 or 5 days. Food intake was reduced by 27 and 44% (both P<0.001) for the 5 and 25 pmol/kg-min groups. respectively, in the 2-day experiment and was decreased by 14% (P<0.01) and 24% (P<0.001), respectively, in the 5-day experiment. Body weight was significantly decreased in a dose-dependent fashion. In the 2-day experiment, norepinephrine increased in the hypothalamus in the 5 pmol IAPP/kg-min group, and neurotensin increased in the hippocampus in the 25 pmol/kg-min rats (both P<0.05). In the 5-day, 5 pmol/kg-min rats, 5-hydroxyindoleacetic acid (5-HIAA) increased in the hypothalmus and cholecystokinin (CCK) increased in the striatum (both P<0.05). In the 5-day, 25 pmol/kg-min group, neuropeptide Y (NPY) increased in the hypothalamus (P<0.01) and CCK increased in the hypothalmus and striatum (both P<0.05). The present study confirms that IAPP is a potent anorectic peptide at low doses and suggests that IAPP not. only affects classical neurotransmitters in the brain but also alters concentrations of neuropeptides known to he involved in food intake. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:391 / 398
页数:8
相关论文
共 42 条
[1]  
ALWARK A, 1987, EUR J PHARMACOL, V135, P307
[2]   Effects of acute and chronic infusion of islet amyloid polypeptide on food intake in rats [J].
Arnelo, U ;
Blevins, JE ;
Larsson, J ;
Permert, J ;
Westermark, P ;
Reidelberger, RD ;
Adrian, TE .
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 1996, 31 (01) :83-89
[3]   Chronic low dose islet amyloid polypeptide infusion reduces food intake, but does not influence glucose metabolism, in unrestrained conscious rats: Studies using a novel aortic catheterization technique [J].
Arnelo, U ;
Permert, J ;
Larsson, J ;
Reidelberger, RD ;
Arnelo, C ;
Adrian, TE .
ENDOCRINOLOGY, 1997, 138 (10) :4081-4085
[4]   Sufficiency of postprandial plasma levels of islet amyloid polypeptide for suppression of feeding in rats [J].
Arnelo, U ;
Reidelberger, R ;
Adrian, TE ;
Larsson, J ;
Permert, J .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 1998, 275 (05) :R1537-R1542
[5]   Chronic infusion of islet amyloid polypeptide causes anorexia in rats [J].
Arnelo, U ;
Permert, J ;
Adrian, TE ;
Larsson, J ;
Westermark, P ;
Reidelberger, RD .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 1996, 271 (06) :R1654-R1659
[6]   SYNTHESES, STRUCTURES AND ANORECTIC EFFECTS OF HUMAN AND RAT AMYLIN [J].
BALASUBRAMANIAM, A ;
RENUGOPALAKRISHNAN, V ;
STEIN, M ;
FISCHER, JE ;
CHANCE, WT .
PEPTIDES, 1991, 12 (05) :919-924
[7]   Differential permeability of the blood-brain barrier to two pancreatic peptides: Insulin and amylin [J].
Banks, WA ;
Kastin, AJ .
PEPTIDES, 1998, 19 (05) :883-889
[8]   Brain regions where cholecystokinin suppresses feeding in rats [J].
Blevins, JE ;
Stanley, BG ;
Reidelberger, RD .
BRAIN RESEARCH, 2000, 860 (1-2) :1-10
[9]   IN-VIVO CENTRAL ACTIONS OF RAT AMYLIN [J].
BOUALI, SM ;
WIMALAWANSA, SJ ;
JOLICOEUR, FB .
REGULATORY PEPTIDES, 1995, 56 (2-3) :167-174
[10]   EFFECTS OF MEAL INGESTION ON PLASMA AMYLIN CONCENTRATION IN NIDDM AND NONDIABETIC HUMANS [J].
BUTLER, PC ;
CHOU, J ;
CARTER, WB ;
WANG, YN ;
BU, BH ;
CHANG, D ;
CHANG, JK ;
RIZZA, RA .
DIABETES, 1990, 39 (06) :752-756