Autoradiographic localization of 5-HT(3) receptor ligand binding in the cat brainstem.
The distribution of binding in the cat brainstem of two 5-HT(3) receptor radioligands, [(3)H]BRL 43694 and [(3)H]GR 65630, was investigated using in vitro quantitative receptor autoradiography. The cat has been used extensively in previous investigations which studied the details of the connections and neurochemistry of the dorsal vagal complex. This caudal brainstem region is the site of heaviest binding of 5-HT(3) receptor radioligands in the central nervous system of those species investigated to date. Thus, it was of interest to determine how the distribution of 5-HT(3) receptor sites could be correlated with the known detailed anatomy of the cat dorsal vagal complex. The highest levels of displaceable binding of both radioligands were seen in the subnucleus gelatinosus of the solitary nucleus which is the principal site of termination of gastric vagal afferent fibres. In addition, lower levels of displaceable binding were seen in the area postrema, other subdivisions of the solitary nucleus and the dorsal motor nucleus of the vagus all of which receive a correspondingly much smaller vagal input. Binding was also seen in the nucleus of the tract of the spinal trigeminal nerve which, like the dorsal vagal complex receives dense sensory innervation. There was no difference in the distribution of binding of the two ligands studied. Our findings are consistent with the hypothesis that 5-HT(3) receptors are located on sensory afferent terminals which may be important in the control of, amongst other things, emesis and the genesis of migraine.
Reynolds
D J
DJ
MRC Unit and University Department of Clinical Pharmacology, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, England.
Leslie
R A
RA
Grahame-Smith
D G
DG
Harvey
J M
JM