Actions of the anthelmintic ivermectin on the pharyngeal muscle of the parasitic nematode, Ascaris suum

被引:79
作者
Brownlee, DJA
HoldenDye, L
Walker, RJ
机构
[1] Pharmacology Group, Division of Cell Sciences, University of Southampton
关键词
Ascaris suum; nematode; pharynx; ivermectin; gamma-aminobutyric acid (GABA); glutamate;
D O I
10.1017/S0031182097001601
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
The anthelmintic ivermectin has a number of effects on nematodes which result in changes in behaviour, particularly locomotion, including paralysis and an inhibition of feeding. This paper describes the application of an in vitro pharmacological approach to further delineate the action of ivermectin on feeding behaviour. Contraction of Ascaris suum pharyngeal muscle was monitored using a modified pressure transducer system which detects changes in intrapharyngeal pressure and therefore contraction of the radial muscle of the pharynx. The pharynx did not contract spontaneously. However, serotonin (5-HT, 100 mu M) stimulated rhythmic contractions and relaxations (pumping) at a frequency of 0.5 Hz. gamma-Aminobutyric acid (GABA) and glutamic acid inhibited the pumping elicited by 5-HT. The duration of inhibition was concentration dependent (1-1000 mu M) with a threshold of 1 mu M and 10 mu M respectively (n = 8). Ivermectin also inhibited pharyngeal pumping (1-1000 nM). At lower concentrations, ivermectin (1-10 pM) potentiated the GABA and glutamate inhibition, so that inhibition occurred at concentrations which were below threshold in the absence of ivermectin. These data provide evidence that the pharynx is a site for the action of ivermectin. Thus interruption of pharyngeal processes such as, feeding, regulation of hydrostatic pressure and secretion mag. provide a new site of anthelmintic action.
引用
收藏
页码:553 / 561
页数:9
相关论文
共 28 条
[1]   EXPRESSION OF A GLUTAMATE-ACTIVATED CHLORIDE CURRENT IN XENOPUS-OOCYTES INJECTED WITH CAENORHABDITIS-ELEGANS RNA - EVIDENCE FOR MODULATION BY AVERMECTIN [J].
ARENA, JP ;
LIU, KK ;
PARESS, PS ;
SCHAEFFER, JM ;
CULLY, DF .
MOLECULAR BRAIN RESEARCH, 1992, 15 (3-4) :339-348
[2]   EFFECTS OF STARVATION AND NEUROACTIVE DRUGS ON FEEDING IN CAENORHABDITIS-ELEGANS [J].
AVERY, L ;
HORVITZ, HR .
JOURNAL OF EXPERIMENTAL ZOOLOGY, 1990, 253 (03) :263-270
[3]   Nematode neuropeptides: Localization, isolation and functions [J].
Brownlee, DJA ;
Fairweather, I ;
HoldenDye, L ;
Walker, RJ .
PARASITOLOGY TODAY, 1996, 12 (09) :343-351
[4]   IMMUNOCYTOCHEMICAL DEMONSTRATION OF PEPTIDERGIC AND SEROTONINERGIC COMPONENTS IN THE ENTERIC NERVOUS-SYSTEM OF THE ROUNDWORM, ASCARIS-SUUM (NEMATODA, ASCAROIDEA) [J].
BROWNLEE, DJA ;
FAIRWEATHER, I ;
JOHNSTON, CF ;
SHAW, C .
PARASITOLOGY, 1994, 108 :89-103
[5]   THE ACTION OF SEROTONIN AND THE NEMATODE NEUROPEPTIDE KSAYMRFAMIDE ON THE PHARYNGEAL MUSCLE OF THE PARASITIC NEMATODE, ASCARIS-SUUM [J].
BROWNLEE, DJA ;
HOLDENDYE, L ;
FAIRWEATHER, I ;
WALKER, RJ .
PARASITOLOGY, 1995, 111 :379-384
[6]  
BYERLY L, 1979, J PHYSIOL-LONDON, V288, P263
[7]  
CAMPBELL W C, 1985, Parasitology Today, V1, P10, DOI 10.1016/0169-4758(85)90100-0
[8]  
Campbell WC, 1989, IVERMECTIN ABAMECTIN
[9]  
CULLY DF, 1991, MOL PHARMACOL, V40, P326
[10]   CLONING OF AN AVERMECTIN-SENSITIVE GLUTAMATE-GATED CHLORIDE CHANNEL FROM CAENORHABDITIS-ELEGANS [J].
CULLY, DF ;
VASSILATIS, DK ;
LIU, KK ;
PARESS, PS ;
VANDERPLOEG, LHT ;
SCHAEFFER, JM ;
ARENA, JP .
NATURE, 1994, 371 (6499) :707-711