Regulatory role of 5-HT and muscarinic receptor antagonists on the migrating myoelectric complex in rats

被引:14
作者
Axelsson, LG
Wallin, B
Gillber, PG
Sjöberg, B
Söderberg, C
Hellström, PM
机构
[1] Karolinska Inst, Karolinska Hosp, Dept Internal Med, Sect Gastroenterol & Hepatol, SE-17176 Stockholm, Sweden
[2] Pharmacia AB, Dept Pharmacol, S-75182 Uppsala, Sweden
[3] Pharmacia AB, Dept Med Chem, S-75182 Uppsala, Sweden
关键词
antimuscarinic; 5-HT receptor; gastrointestinal motility; muscarinic receptor; (rat);
D O I
10.1016/S0014-2999(03)01637-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The 5-HT3 and 5-HT4 receptor antagonists alosetron and piboserod, and the muscarinic receptor antagonists PNU-171990A (2(diisopropylamino)ethyl 1-phenylcyclopentanecarboxylate, hydrochloride) and PNU-174708A (2-(diisopropylamino)ethyl 1-phenylcyclohexanecarboxylate) were studied by electromyography, defining the migrating myoelectric complex (MMC) after i.v. administration in conscious rats. Alosetron prolonged the MMC cycle length from 16.6 to maximally 30.4 min at the dose 0.5 mg kg(-1). Piboserod promptly abolished MMC pattern and prolonged cycle length from 16.5 to >60 min at 0.5 mg kg(-1). PNU-171990A and PNU-174708A had no effect on basal cycle length up to a dose of 20 mg kg(-1). In controls, saline did not change the MMC pattern, while L-hyoscyamine at the same dose, 20 mg kg(-1), prolonged cycle length from 17.6 to 29.0 min. None of the drugs affected duration or propagation velocity of phase III of MMC. Blockade of 5-HT4 receptors seems to exert a powerful inhibitory effect on motility, 5-HT3 receptor blockade is less efficient and muscarinic receptor blockade has low efficacy. (C) 2003 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:211 / 218
页数:8
相关论文
共 39 条
[1]   INFLUENCE OF FASTING AND BOMBESIN-INDUCED MYOELECTRIC ACTIVITY ON THE TRANSIT OF SMALL-INTESTINAL CONTENTS IN THE RAT [J].
ALSAFFAR, A ;
HELLSTROM, PM ;
NYLANDER, G ;
ROSELL, S .
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 1984, 19 (04) :541-546
[3]   Electromyographic studies of the gastro-intestinal tract I. The correlation between mechanical movement and changes in electrical potential during rhythmic contraction of the intestine [J].
Berkson, J ;
Baldes, EJ ;
Alvarez, WC .
AMERICAN JOURNAL OF PHYSIOLOGY, 1932, 102 (03) :683-692
[4]   Characteristics of fasting and fed myoelectric activity in rat small intestine: Evaluation by computer analysis [J].
Branstrom, R ;
Hellstrom, PM .
ACTA PHYSIOLOGICA SCANDINAVICA, 1996, 158 (01) :53-62
[5]   Effects of alosetron on spontaneous migrating motor complexes in murine small and large bowel in vitro [J].
Bush, TG ;
Spencer, NJ ;
Watters, N ;
Sanders, KM ;
Smith, TK .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2001, 281 (04) :G974-G983
[6]   Pharmacology and clinical experience with alosetron [J].
Camilleri, M .
EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2000, 9 (01) :147-159
[7]   MUSCARINIC RECEPTORS - CHARACTERIZATION, COUPLING AND FUNCTION [J].
CAULFIELD, MP .
PHARMACOLOGY & THERAPEUTICS, 1993, 58 (03) :319-379
[8]  
Clayton NM, 1999, NEUROGASTROENT MOTIL, V11, P207
[9]   Irritable bowel syndrome - New agents targeting serotonin receptor subtypes [J].
De Ponti, F ;
Tonini, M .
DRUGS, 2001, 61 (03) :317-332
[10]  
DROSSMAN DA, 1999, GUT, V45, pR1