EVIDENCE FOR PRESYNAPTIC 5-HYDROXYTRYPTAMINE3 RECOGNITION SITES ON VAGAL AFFERENT TERMINALS IN THE BRAIN-STEM OF THE FERRET

被引:76
作者
LESLIE, RA
REYNOLDS, DJM
ANDREWS, PLR
GRAHAMESMITH, DG
DAVIS, CJ
HARVEY, JM
机构
[1] UNIV OXFORD, MRC UNIT, OXFORD OX2 6HE, ENGLAND
[2] UNIV OXFORD, RADCLIFFE INFIRM, DEPT CLIN PHARMACOL, OXFORD OX2 6HE, ENGLAND
[3] ST GEORGE HOSP, SCH MED, DEPT PHYSIOL, LONDON SW17 0RE, ENGLAND
关键词
D O I
10.1016/0306-4522(90)90060-H
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Antagonists acting at the 5-hydroxytryptamine3 receptor are potent anti-emetic agents in cases of cytotoxic- and radiation-induced vomiting, and binding sites for these compounds have been described in brainstem areas known to be involved in mediation of nausea and vomiting. We have used autoradiography to examine the distribution of one of these antagonists, [3H]granisetron in the caudal brainstem of the ferret, a commonly used animal model for physiological investigations of emesis. The highest density of binding sites was found to be in the dorsomedial region of the nucleus of the solitary tract, the principal terminus for gastric vagal afferent fibres. Lower levels of binding were observed in the area postrema and the dorsal motor nucleus of the vagus. Following unilateral nodose ganglion excision, displaceable binding of [3H]granisetron in the nucleus of the solitary tract was attenuated on the ipsilateral side by 65%. Bilateral subdiaphragmatic vagotomy abolished binding of [3H]granisetron in the entire dorsal vagal complex. These results provide strong circumstantial evidence that 5-hydroxytryptamine3 receptors are located on vagal afferent terminals in the ferret brainstem. © 1990.
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页码:667 / 673
页数:7
相关论文
共 36 条
[1]   NEUROPHARMACOLOGY OF EMESIS INDUCED BY ANTI-CANCER THERAPY [J].
ANDREWS, PLR ;
RAPEPORT, WG ;
SANGER, GJ .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1988, 9 (09) :334-341
[2]   EVIDENCE FOR AN EXTRA-ABDOMINAL SITE OF ACTION FOR THE 5-HT3 RECEPTOR ANTAGONIST BRL24924 IN THE INHIBITION OF RADIATION-EVOKED EMESIS IN THE FERRET [J].
ANDREWS, PLR ;
HAWTHORN, J .
NEUROPHARMACOLOGY, 1987, 26 (09) :1367-1370
[3]  
ANDREWS PLR, 1986, PROG BRAIN RES, V67, P65
[4]  
ANDREWS PLR, 1986, J PHYSIOL-LONDON, V382, pP187
[5]  
ANDREWS PLR, 1990, IN PRESS J PHYSL
[6]   [H-3] ZACOPRIDE - LIGAND FOR THE IDENTIFICATION OF 5-HT3 RECOGNITION SITES [J].
BARNES, NM ;
COSTALL, B ;
NAYLOR, RJ .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 1988, 40 (08) :548-551
[7]   CONTRIBUTION OF THE VAGUS NERVE TO ANGIOTENSIN-II BINDING-SITES IN THE CANINE-MEDULLA [J].
DIZ, DI ;
BARNES, KL ;
FERRARIO, CM .
BRAIN RESEARCH BULLETIN, 1986, 17 (04) :497-505
[8]   CONNECTIONS OF A VAGAL COMMUNICATING BRANCH IN THE FERRET .2. CENTRAL PROJECTIONS [J].
FITZAKERLEY, JL ;
LUCIER, GE .
BRAIN RESEARCH BULLETIN, 1988, 20 (04) :479-486
[9]   TRANSGANGLIONIC DEGENERATION IN TRIGEMINAL PRIMARY SENSORY NEURONS [J].
GRANT, G ;
ARVIDSSON, J .
BRAIN RESEARCH, 1975, 95 (2-3) :265-279
[10]   SPECULATIONS ON THE STRUCTURE-FUNCTION RELATIONSHIP FOR VAGAL AND SPLANCHNIC AFFERENT ENDINGS SUPPLYING THE GASTROINTESTINAL-TRACT [J].
GRUNDY, D .
JOURNAL OF THE AUTONOMIC NERVOUS SYSTEM, 1988, 22 (03) :175-180