Evidence for presynaptic 5-hydroxytryptamine3 recognition sites on vagal afferent terminals in the brainstem of the ferret.
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.
Leslie
R A
RA
Oxford University-Beecham Centre for Applied Neuropsychobiology, U.K.
Reynolds
D J
DJ
Andrews
P L
PL
Grahame-Smith
D G
DG
Davis
C J
CJ
Harvey
J M
JM
D000344:Afferent Pathways / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001933:Brain Stem / Q000378:metabolism*; D003714:Denervation; D005289:Ferrets; D017829:Granisetron; D007191:Indazoles / Q000378:metabolism; D009411:Nerve Endings / Q000378:metabolism*; D009620:Nodose Ganglion / Q000502:physiology; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism; D013153:Splanchnic Nerves / Q000502:physiology; D013569:Synapses / Q000378:metabolism*; D014630:Vagus Nerve / Q000378:metabolism*
D017829:Granisetron; D007191:Indazoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists